Brief Biography of 洪 実.
洪 実(こうみのる)略歴
1961年大阪府生まれ。2004年米国市民権取得。現在、米国メリーランド州ボルチモア在住。1983年、慶應義塾大学医学部在学中より研究活動を開始、1986年に卒業、1991年に博士号。1988年、ERATO古澤発生遺伝子プロジェクトに参画、1991年にグループリーダー。1992年に渡米し、ウェイン州立大学助教授に着任、1996年に准教授(終身在職権)。1998年から2011年まで、米国国立衛生研究所(NIH)国立老化研究所(NIA)にて上級研究員(終身在職権)と発生老化ゲノム学部門長を務めた。2012年、慶應義塾大学医学部坂口記念システム医学講座教授に就任、2022年に退職、名誉教授となった。専門はシステム医学、発生生物学、幹細胞生物学、ゲノム科学。システム思考を基盤として、大規模実験と情報科学を統合し、遺伝子ネットワークの視点から生命システムを包括的に理解する研究を先導してきた。加えて、Elixirgen(2012年)、Elixirgen Scientific(現 Ricoh Biosciences、2016年)、Elixirgen Therapeutics(2017年)を共同創業し、Chief Scientific Officer を務めるなど、研究成果の社会実装にも尽力。170編を超える学術論文を発表し、ハリソン内科学 第17〜19版「幹細胞生物学」の章を執筆。病に苦しむ人々の治療法の開発を、生涯を通じた志としている。
■ CURRENT POSITIONS
• エリクサジェン・セラピューティックス社 最高科学責任者
• 慶應義塾大学名誉教授
■ OTHER BIOGRAPHICAL LINKS
• Academia Aeterna (English page) https://academia-aeterna.org/m/?MinoruKo
• Reproductive Biomedicine Online https://www.rbmojournal.com/article/S1472-6483(10)60852-8/fulltext
• LinkedIn https://www.linkedin.com/in/minoru-ko-b46374106
• Keio Researchers Information System https://k-ris.keio.ac.jp/html/100001708_en.html
• Google Scholar https://scholar.google.com/citations?user=f4D7YvQAAAAJ&hl=en
■ NOTABLE CONTRIBUTIONS TO SCIENCE
• システム思考・システム生物学・システム医学
• 正のフィードバックによる遺伝子発現制御
• 確率的遺伝子発現
• 均一化 cDNA ライブラリー
• マウス全遺伝子カタログ
• NIA 15K Mouse cDNA Clone Set
• NIA 7.4K Mouse cDNA Clone Set
• NIA マウス全遺伝子マイクロアレイ
• Agilent マウス全遺伝子オリゴヌクレオチド・マイクロアレイ
• マウス着床前胚における網羅的遺伝子発現パターン
• バイオインフォマティクス・ツール
• マウスにおける全 mRNA の半減期
• マウス ES 細胞およびヒト ES 細胞における転写因子の体系的操作
• 転写因子 mRNA を用いたヒト ES/iPS 細胞の分化誘導
• T細胞ワクチンとしての制御可能自己複製RNA(c-srRNA)ベクター
• ZSCAN4 の発見とその機能解析
● システム思考・システム生物学・システム医学(1985年〜)
私の研究は、システム思考を基盤としており、大規模実験科学と情報科学的手法を統合することによって、生物学的システムを全体として理解することを目指している。とりわけ、全遺伝子から成るネットワークという視点を重視してきた。研究初期には、遺伝子制御ネットワークの計算機シミュレーションに取り組んだが、ほどなくして、遺伝子制御の仕組み、遺伝子間相互作用、ネットワーク形成、ならびにその構造と動態に関する定量的データが著しく不足していることを痛感した。こうした初期の試みについては、後述の「正のフィードバックによる遺伝子発現制御」および「確率的遺伝子発現」の項で詳述している。
私が早い段階から構想していた重要な基盤技術の一つは、すべての遺伝子の発現量を一度に測定する方法の確立であった。1988年から、Pan-blottingと名付け、この技術の開発を本格的に開始した。このような技術を実現するため、私自身のみならず、研究室メンバーや共同研究者とともに、マウスの全遺伝子を対象とする体系的かつゲノム規模の大規模解析を推進してきた。これらの遺伝子の中には、胚や幹細胞においてのみ機能するものが少なくなく、そのため研究は発生生物学、幹細胞生物学、ゲノム科学の接点に重点を置くものとなった。私たちはこの研究領域を developmental genomics(発生ゲノム学)、あるいは embryogenomics と呼んできた。これらの取り組みについては、「均一化 cDNA ライブラリー」「マウス全遺伝子カタログ」「NIA 15K Mouse cDNA Clone Set」「NIA 7.4K Mouse cDNA Clone Set」「NIA マウス全遺伝子マイクロアレイ」「Agilent マウス全遺伝子オリゴヌクレオチド・マイクロアレイ」「マウス着床前胚における網羅的遺伝子発現パターン」「バイオインフォマティクス・ツール」「マウスにおける全 mRNA の半減期」「マウス ES 細胞およびヒト ES 細胞における転写因子の体系的操作」の各項において詳述している。
私は、生涯の目標として、病に苦しむ人々のための有効な治療法を開発することを志しており、これらの研究を常に医学研究および治療応用の観点から位置づけてきた。例えば、「正のフィードバックによる遺伝子発現制御」に関する研究は、「T細胞ワクチンとしての制御可能自己複製RNA(c-srRNA)ベクター」の開発へとつながった。また、「マウス ES 細胞およびヒト ES 細胞における転写因子の体系的操作」に関する研究は、「転写因子 mRNA を用いたヒト ES/iPS 細胞の分化誘導」の開発につながり、これは再生医療への直接的応用が期待される。mRNA技術の治療応用は、現在の私の重点研究領域の一つとなっている。さらに、「マウス着床前胚における網羅的遺伝子発現パターン」に関する体系的大規模解析の研究からは、2000年代初頭にZSCAN4遺伝子の発見へと至った。この発見は、その後、テロメア伸長、ゲノム完全性、核型安定性、幹細胞老化および若返りにおける機能の解明へと発展し、これらについては「ZSCAN4 の発見とその機能解析」に記している。近年は、とりわけZSCAN4の治療応用に一層注力している。
Key References:
• Takano, Ko (1985). Enhancer sequences for gene expression regulation.
• Ko (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs. 考察からの引用:「私は、本論文で示した手法によって、あらゆる生物の一生を通じて発現する遺伝子の全セットのカタログを作製できるようになると考えている。このカタログは、mRNAの放射標識cDNAコピーをプローブとして用いることにより、大部分の遺伝子の発現レベルを同時に測定するために利用でき、さらに組織特異的に発現する遺伝子の同定を可能にするであろう。これらの応用においては、完全長cDNA分子よりも、ここで示した短いcDNA断片を用いる方がより適切であることを指摘しておく価値がある。というのも、3′末端断片の高い配列特異性によって、異なるcDNA分子種間の交差ハイブリダイゼーションが排除されるはずだからである。」
https://pubmed.ncbi.nlm.nih.gov/2216762/
• Schlessinger, Ko (1998). Developmental Genomics and Its Relation to Aging.
https://pubmed.ncbi.nlm.nih.gov/10348638/
• Ko (2001). Embryogenomics: developmental biology meets genomics.
https://pubmed.ncbi.nlm.nih.gov/11711195/
• Ko (2004). Embryogenomics of preimplantation mammalian development: Current Status.
https://pubmed.ncbi.nlm.nih.gov/14972105/
• Tanaka et al. (2004). Genomic approaches to stem cell biology.
• VanBuren, Ko (2004). Principles and Application of Embryogenomics.
• Aiba et al. (2006). Genomic approaches to early embryogenesis and stem cell biology.
https://pubmed.ncbi.nlm.nih.gov/17123228/
• Ko (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions.
https://pubmed.ncbi.nlm.nih.gov/15820015/
• Ko (2006). Expression profiling of the mouse early embryo: Reflections and perspectives.
https://pubmed.ncbi.nlm.nih.gov/16739220/
● 正のフィードバックによる遺伝子発現制御(1989年)
私は、哺乳類細胞において導入遺伝子の発現を増強するために、正のフィードバック・ループを利用することを着想した。グルココルチコイド受容体の産生が自らのシグナル伝達を増幅するように設計することで、従来の系と比べて、基礎発現を非常に低く抑えながら、はるかに強い誘導を実現した。この概念は、まず一過性発現アッセイで実験的に実証され、その後、ゲノムへの組込み後の安定形質転換細胞においても示された。私たちは、人工的な正のフィードバック制御が哺乳類細胞の遺伝子発現に実装可能であることを初めて実証した。この研究は、遺伝子をスイッチとして捉え、その相互連関やフィードバック・ループを探究しようとした最も初期の試みの一つであった。
Key References:
• Ko, Takano (1989). A highly inducible system of gene expression by positive feedback production of glucocorticoid receptors. https://pubmed.ncbi.nlm.nih.gov/2494026/
• Ko et al. (1989). An auto-inducible vector conferring high glucocorticoid-inducibility upon stable transformant cells (1989). https://pubmed.ncbi.nlm.nih.gov/2558971/
● 確率的遺伝子発現(1990年〜2012年)
私は、哺乳類の細胞ひとつひとつには父方由来と母方由来の2コピーしか遺伝子が存在しないことに注目し、単一遺伝子の発現が、単一細胞レベルでどのように制御されているのかを調べたいと考えた。そこで私は、細胞集団においてLacZ染色により1コピーの遺伝子の発現を可視化できるトランスジーン、すなわちβ-ガラクトシダーゼを用いることを着想した。この実験により、私たちは遺伝子発現が確率的過程であることを初めて発見した。この一連の研究は、現在ではこの分野の基礎を築いたものとして認識されており、同分野における最も初期の一群の論文とみなされている。例えば、Raj と van Oudenaarden は、2008年の Cell 誌の総説において、「単一細胞における発現レポーターを用いて、発現変動性の確率論的基盤を検討した最初期の研究の一つは、Ko ら(1990)による先駆的研究である」と述べている。
私はまた、この確率的遺伝子発現制御について理論的枠組みを構築し、コンピュータ・シミュレーションも行った。このモデルでは、転写因子が遺伝子にランダムに結合し、また解離する。転写複合体が結合しているとき(“on”状態)には、メッセンジャーRNA(mRNA)が産生される。一方、この複合体が存在しないとき(“off”状態)には、転写は起こらず、mRNAも産生されない。転写因子量が増加すると、off状態からon状態へ切り替わる確率が高まり、on状態の細胞が増え、その結果として細胞集団として遺伝子発現レベルが上昇する。重要な点として、このモデルは、もし“on”状態の複合体が安定であれば、個々の細胞は細胞集団内で不均一、すなわちばらつきのある遺伝子発現レベルを示すと予測した。Larson、Singer、Zenklusen は、2009年の Trends in Cell Biology 誌の総説において、「この遺伝子誘導モデルは、しばしば Random Telegraph model と呼ばれるが、最初に Ko(1991)によって提唱された」と記している。
Key References:
• Ko, Nakauchi, Takahashi (1990). The dose-dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates.
https://pubmed.ncbi.nlm.nih.gov/2167833/
• Ko (1991). A stochastic model for gene induction.
https://pubmed.ncbi.nlm.nih.gov/1787735/
• Ko (1992). Induction mechanism of a single gene molecule: Stochastic or Deterministic?
https://pubmed.ncbi.nlm.nih.gov/1637366/
• Yang, Ko (2012). Stochastic modeling for the expression of a gene regulated by competing transcription factors.
https://pubmed.ncbi.nlm.nih.gov/22431973/
● 均一化 cDNA ライブラリー(別名 正常化 cDNA ライブラリー)(1990年、1994年)
大規模な遺伝子カタログ化および網羅的遺伝子発現解析を可能にするため、私は1986年頃から 均一化 cDNA ライブラリー の構築法の開発に着手し、1990年にその成果を発表した。この方法により、従来の cDNA ライブラリー中に極めて不均一な頻度で存在する cDNA(遺伝子)クローンを、初めて均等化することが可能となった。本手法は、短い二本鎖 cDNA の自己再会合と、それに続く PCR 回収を利用するものであり、存在量の偏りを大幅に低減し、希少転写産物(mRNA)の検出を飛躍的に容易にした。また、均一化 cDNA ライブラリー に含まれる遺伝子を同定するため、私は184個の cDNA クローンを手作業で塩基配列決定した。1990年のこの論文は、後に expressed sequence tag(EST)解析として知られるようになる大規模 cDNA シーケンシング研究の最初期の例の一つであったと考えられる。
その後、私たちはこの手法を発生過程にあるマウス胚に適用し、均一化 cDNA ライブラリー が、冗長性を大幅に低減しつつ、組織特異的遺伝子をより適切に含む広範な「全 cDNA カタログ」に近似し得ることを示した。興味深いことに、高度に均一化された cDNA ライブラリーに含まれる独立した遺伝子数は約15,000であり、現在の一般的な見解である20,000〜25,000遺伝子という数に近いものであった。これは、哺乳類の遺伝子総数が当時広く想定されていた35,000〜100,000よりも少ないことを示唆する、最も早い時期の実験的証拠の一つであったと考えられる。
Key References:
• Ko (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs.
https://pubmed.ncbi.nlm.nih.gov/2216762/
• Takahashi, Ko (1994). Towards a whole cDNA catalog: an equalized cDNA library from mouse embryos.
https://pubmed.ncbi.nlm.nih.gov/7829072/
●マウス全遺伝子カタログ(1990年〜2003年)
ウェイン州立大学へ移って以降も引き続き、私は「マウス全遺伝子カタログ」の構築を目標として、ヒト材料からは入手が困難な細胞や組織を対象に、cDNA ライブラリーの作製を継続した。自動DNAシーケンサーが利用可能になると、cDNA クローンの塩基配列解析も継続して進めた。さらに、cDNA の 3′-UTR に高頻度に認められる配列多型を利用した、迅速な PCR ベースの遺伝子マッピング法も開発した(1993年、1994年)。最初のNIH グラントの支援のもと、まず着床周辺期の胚外組織に着目し、3,186 個の EST を作製するとともに、マウスゲノム上に 155 個の新規遺伝子(Wsuマーカー)をマッピングした(1998年)。さらに、ERATO土居バイオアシンメトリープロジェクトの支援を受け、マウス着床前胚の全発生段階〔未受精卵、受精卵(zygote)、2細胞期胚、4細胞期胚、8細胞期胚、桑実胚、胚盤胞〕から cDNA ライブラリーを作製した(2000年)。その後、大規模シーケンシングを実施し、25,438 個の EST を取得し、9,718 個のユニーク遺伝子を同定するとともに、798 個の新規遺伝子(Ertdマーカー)をマウスゲノム上にマッピングした(2000年)。
その後、米国国立衛生研究所(NIH)国立老化研究所(NIA)へ移ってからも、 cDNA ライブラリーの作製と個々の cDNA クローンの塩基配列解析を継続した。引き続き、マウス胚、新生仔卵巣、胚性幹細胞、組織幹細胞など、ヒトからは入手が困難なマウスの細胞・組織に重点を置いた。NIA では、このプロジェクトはさらに拡大し、私は NIA Mouse cDNA Project の主任研究者(Principal Investigator, 1998年〜2004年)を務めた。本プロジェクトは、以下のような研究リソースを全世界の研究者に無償で共有することにより、研究コミュニティに貢献した。すなわち、約40万件の cDNA 配列情報(EST)を公共データベース(dbEST および GenBank)に登録したが、これは当時公共データベース(NCBI/dbEST)に登録されていたマウス cDNA 配列総数 4,218,080 件の約10%に相当した。特に、着床前胚由来のマウス cDNA クローン/配列については、当時収集されていた総数 158,039 件のうち 89,440 件を本プロジェクトが占め、最大の寄与を果たした。また、約30万個の cDNA クローンを自由に配布されるように American Type Culture Collection(ATCC)に寄託した。さらに、NIH 全体で進められた Mammalian Gene Collection(MGC)にも貢献し、当時登録されていた全 17,707 個の完全長 cDNA クローン/遺伝子のうち 716 個(約4%)は、私たちの Mouse cDNA Project に由来するものであった。
Key References:
• Takahashi, Ko (1993). The short 3′-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome.
https://pubmed.ncbi.nlm.nih.gov/8486351/
• Ko et al. (1994). Genetic mapping of 40 cDNA clones on the mouse genome by PCR.
https://pubmed.ncbi.nlm.nih.gov/8043949/
• Ko et al. (1998). Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome.
https://pubmed.ncbi.nlm.nih.gov/9811942/
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Piao et al. (2001). Construction of long-transcript enriched cDNA libraries from submicrogram amounts of total RNAs by a universal PCR amplification method.
https://pubmed.ncbi.nlm.nih.gov/11544199/
• Sharov et al. (2003). Transcriptome Analysis of Mouse Stem Cells and Early Embryos.
https://pubmed.ncbi.nlm.nih.gov/14691545/
• Carter et al. (2003). The NIA cDNA Project in mouse stem cells and early embryos.
https://pubmed.ncbi.nlm.nih.gov/14744099/
• Ko (2004). Embryogenomics of preimplantation mammalian development: Current Status.
https://pubmed.ncbi.nlm.nih.gov/14972105/
• Tanaka, Ko (2004). A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst.
https://pubmed.ncbi.nlm.nih.gov/15196723/
• Gerhard et al., (2004). The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
https://pubmed.ncbi.nlm.nih.gov/15489334/
● NIA 15K Mouse cDNA Clone Set(2000年)および NIA 7.4K Mouse cDNA Clone Set(2002年)
私の研究室は、15,000個のユニークなマウス遺伝子から成る NIA 15K Mouse cDNA Clone Set と、さらに7,400個のユニークなマウス遺伝子から成る NIA 7.4K Mouse cDNA Clone Set を確立し、公共研究資源として公開・配布した。これらを合わせることにより、cDNA 形式においてマウス遺伝子のほぼ全体を網羅することが可能となった。これらの cDNA クローンセットは、公共研究資源として、ライセンスや利用制限を設けることなく、NIH 内の11を超える研究所・センターならびに世界各国の135の大学・研究機関に無償で提供された。さらに、これらの cDNA クローンは、網羅的遺伝子発現プロファイリングのための cDNA マイクロアレイ作製にも活用された。
Key References
• Tanaka et al. (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.
https://pubmed.ncbi.nlm.nih.gov/10922068/
• Kargul et al. (2001). Verification and initial annotation of the NIA mouse 15K cDNA clone set.
https://pubmed.ncbi.nlm.nih.gov/11326268/
• VanBuren et al. (2002). Assembly, verification, and initial annotation of the NIA mouse 7.4K cDNA clone set.
https://pubmed.ncbi.nlm.nih.gov/12466305/
● NIA マウス全遺伝子マイクロアレイ(2000年)
私の研究室は、15,000個のユニークな cDNA クローン(NIA 15K Mouse cDNA Clone Set)をナイロンメンブレン上にスポットすることにより、NIA Mouse Whole cDNA Microarrays を作製した(2000年)。私たちは、このマイクロアレイが、マウス胚性幹細胞(ES細胞)、栄養膜幹細胞(TS細胞)、およびマウス胎児線維芽細胞(MEF細胞)における網羅的遺伝子発現プロファイリングに有用であることを示した。その結果、これら各細胞型に特徴的な分子シグネチャーを同定した。その後、NIA 7.4K Mouse cDNA Clone Set を追加することにより、cDNA マイクロアレイの網羅性をさらに拡張した。これらのマイクロアレイは、NIA の研究費採択者にも配布された。
Key References
• Tanaka et al. (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.
https://pubmed.ncbi.nlm.nih.gov/10922068/
● Agilent マウス全遺伝子オリゴヌクレオチド・マイクロアレイ(2003年、2005年)
Agilent Technologies社とのNIH CRADA 契約のもと、私の研究室は、マウス全遺伝子を代表する60-mer配列を設計することにより、マウスin situ合成60-merオリゴヌクレオチド・マイクロアレイの開発を支援した。マウス22K全遺伝子アレイ(22,000遺伝子フィーチャーを搭載、2003年にリリース)およびマウス44K全遺伝子アレイ(44,000遺伝子フィーチャーを搭載、2005年にリリース)は、Agilent Technologies社により製品化され、世界的に広く使用されている。2003年の論文では、わずか2 ngの全RNAからでも高い再現性をもってグローバルな遺伝子発現プロファイリングが可能であることを示した。これにより、初期胚や希少な幹細胞集団のような極めて微量な試料に対しても、グローバルな発現プロファイリングが実行可能となった。2005年の論文では、酵母由来のRNAをスパイクイン・コントロールとして導入し、相対的な発現差のみならず、転写産物の絶対量を定量的に推定できるようにした。このシステムを用いて、私の研究室は、哺乳類のトランスクリプトームが非常に複雑であり、多くの遺伝子がごく少数コピーで発現していること、また多くの転写産物が組織や幹細胞型を超えて広く共有されていることを示した。さらに私の研究室は、NIH全体の取り組みの一環として、Agilent Technologies社と協力し、ラット全遺伝子オリゴヌクレオチド・マイクロアレイの開発にも携わった。
Key References
• Carter et al. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.
https://pubmed.ncbi.nlm.nih.gov/12727912/
• Carter et al (2005). Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.
https://pubmed.ncbi.nlm.nih.gov/15998450/
● マウス着床前胚における網羅的遺伝子発現パターン(2000年、2004年)
私の研究室は、マウス着床前胚の全ステージにわたる遺伝子発現について、初めて包括的な全体像を提示した。2000年の研究では、ステージ特異的cDNAライブラリーの大規模EST解析により、9,718遺伝子を構成する25,438個のESTが同定され、哺乳類ゲノムの相当部分が初期胚発生の過程で活性化されていること、また多くの遺伝子が持続的ではなく、ステージ特異的かつ一過性に発現することが明らかとなった。
2004年の研究は、マウス着床前胚を対象とした、マイクロアレイに基づく最初のグローバル遺伝子発現解析であり、2000年の研究をさらに発展させたものであった。この研究により、受精後に母性RNA群が一斉に分解されること、接合子(受精後)ゲノム活性化(ZGA)の主要な波に加え、コンパクションおよび胚盤胞形成に先行する第二の波、すなわち着床前中期遺伝子活性化(MGA)を含む、複数の接合子転写活性化の波が示された(2004、2005年)。この研究は、発生学の教科書 Principles of Development(第5版;Wolpert, Tickle, Arias, Lawrence, Lumsden, Robertson, Meyerowitz, Smith 著)にも取り上げられた。これらの研究を通じて、初期マウス発生を支える全遺伝子レパートリーと、波状的な遺伝子活性化プログラムが明らかにされた。
また私の研究室は、whole-mount in situ hybridization を用いて、マウス胚盤胞における91個の転写因子の空間的発現パターンも明らかにした(2006年)。
Key References:
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Hamatani et al. (2004). Dynamics of global gene expression changes during mouse preimplantation development.
https://pubmed.ncbi.nlm.nih.gov/14723852/
• Ko (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions.
https://pubmed.ncbi.nlm.nih.gov/15820015/
• Yoshikawa et al. (2006). High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization.
https://pubmed.ncbi.nlm.nih.gov/16325481/
● マウスにおける全 mRNA の半減期(2009年)
私の研究室は、胚性幹細胞においてマウス19,977遺伝子のmRNA半減期を測定することにより、哺乳類細胞におけるmRNA安定性に関する最初期のゲノムスケール・データの一つを提供した。その結果、大部分の転写産物は比較的安定であり、半減期の中央値は7.1時間である一方、短寿命mRNAは転写因子、細胞周期関連遺伝子、発生制御因子などの制御性遺伝子に富むことが示された。これに対して、安定なmRNAは、代謝、細胞外マトリックス、細胞骨格、およびタンパク質合成に関わる遺伝子と関連していた。重要な点として、この研究は、mRNA安定性が遺伝子機能よりも転写産物の構造とより強く相関することを示し、エクソン接合部密度を主要な安定化要因として、またAU-rich、PUF、およびCpG関連モチーフを不安定化決定因子として同定した。
Key Reference:
• Sharova et al. (2009). Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/19001483/
● バイオインフォマティクス・ツール(2006年〜)
私の研究室は、マウス遺伝子およびマイクロアレイ解析のためのソフトウェアツール、データベース、ウェブサイトを開発し、NIA/NIH における研究室サーバーを通じて研究コミュニティに無償公開してきた(これらの多くは、研究室の NIH からの移転に伴い、現在は利用できなくなっている)。
• ExAtlas(NIA Array Analysis):マイクロアレイデータの統計解析
• NIA Mouse Gene Index:遺伝子および選択的転写産物に関するデータベース
• CisFinder:ChIP-seq データからの転写因子結合モチーフの同定
• CisView:シス制御モジュールおよび転写因子結合部位の可視化
• Protein Interactions:他種由来情報を移植したマウスタンパク質相互作用データベース
Key References:
• Sharov et al. (2005). A web-based tool for principal component and significance analysis of microarray data.
https://pubmed.ncbi.nlm.nih.gov/15734774/
• Sharov et al. (2005). Genome-wide assembly and analysis of alternative transcripts in mouse.
https://pubmed.ncbi.nlm.nih.gov/15867436/
• Sharov et al. (2006). CisView: a browser and database of cis-regulatory modules predicted in the mouse genome.
https://pubmed.ncbi.nlm.nih.gov/16980320/
• Yellaboina et al. (2008). Prediction of evolutionarily conserved interologs in Mus musculus.
https://pubmed.ncbi.nlm.nih.gov/18842131/
• Sharov, Ko (2009). Exhaustive search for over-represented DNA sequence motifs with CisFinder.
https://pubmed.ncbi.nlm.nih.gov/19740934/
• Sharov et al. (2015). ExAtlas: An interactive online tool for meta-analysis of gene expression data.
https://pubmed.ncbi.nlm.nih.gov/26223199/
● マウス ES 細胞(2009年)およびヒト ES 細胞(2020年)における転写因子の体系的操作
遺伝子制御ネットワークを解明するため、私の研究室は、多能性幹細胞において単一の転写因子(TF)の発現を操作し、その結果生じる全遺伝子の発現変化を測定する体系的プラットフォームを構築した。マウス ES 細胞では、50種類の転写因子を誘導発現可能とし、その後、前述の Agilent Mouse Whole Microarrays を用いて網羅的遺伝子発現解析を行うことにより、特定の転写因子によって制御される遺伝子群の全体像を明らかにするとともに、マウス ES 細胞が特定の細胞系譜・組織系譜へ分化誘導されることを示した(2009年)。その後、転写因子誘導型マウス ES 細胞株の数を、2013年には137株、2016年には185株へと拡張した。これと相補的に行った shRNA による抑制実験からは、少数の因子をノックダウンした場合にのみ大きなトランスクリプトーム変化が生じ、その変化は主として二つの細胞運命軌道に沿って現れることが明らかとなり、遺伝子制御ネットワークの顕著な頑健性が示された(2013年、2014年)。
さらに、この戦略をヒト ES 細胞へと展開し、714遺伝子を対象とする2,135種類の誘導発現細胞株を構築した。その結果、大規模な形態学的およびトランスクリプトーム解析マップを作成し、複数の発生系譜にわたるヒト細胞分化プログラムをそれぞれ駆動する転写因子群を分類・同定した(2020年)。
Key Resources:
• NIA Transcription factor (TF)-manipulable Mouse ES Cell Bank: 103 TF-manipulable mouse ES cell lines have been made available from Coriell Institute for Medical Research, https://www.coriell.org/0/Sections/Collections/NIA/Mesc.aspx?PgId=691&coll=AG
• Keio Transcription factor (TF)-manipulable Human ES Cell Bank: Cell Lines of TF-manipulated human ES cells: Deposited and available from RIKEN Bioresource Center Cell Bank (search “Minoru Ko” at https://cell.brc.riken.jp/en/ ). Total 2142 cell lines.
• Database for Transcription Factor (TF)-manipulated human ES cell data (linked from the paper) (http://www.systemsmedicine.jp/crest/plasmid/ ).
• Plasmid vectors for mammalian gene expression: Deposited and available from Addgene (search “Minoru Ko” in https://www.addgene.org/ ). Total 43 plasmids.
Key References
• Matoba et al. (2006). Dissecting oct3/4-regulated gene networks in embryonic stem cells by expression profiling.
https://pubmed.ncbi.nlm.nih.gov/17183653/
• Nishiyama et al. (2009). Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/19796622/
• Correa-Cerro et al. (2011). Generation of mouse ES cell lines engineered for the forced induction of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/22355682/
• Nishiyama et al. (2013). Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells.
https://pubmed.ncbi.nlm.nih.gov/23462645/
• Sharov et al., (2014). Chromatin properties of regulatory DNA probed by manipulation of transcription factors.
https://pubmed.ncbi.nlm.nih.gov/24918633/
• Yamamizu et al. (2016). Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines.
https://pubmed.ncbi.nlm.nih.gov/27150017/
• Nakatake et al. (2020). Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors.
https://pubmed.ncbi.nlm.nih.gov/32433964/
● 転写因子 mRNA を用いたヒト ES/iPS 細胞の分化誘導(2013年〜2020年)
私の研究室は、上述した転写因子の体系的操作から得られた網羅的遺伝子発現の相関マトリクスを先駆的に活用し、胚性幹細胞を特定の細胞系譜へ迅速に誘導する転写因子を体系的に同定する手法を開発した。また、合成メッセンジャーRNA(synthetic mRNA, syn-mRNA)を用いて、多能性幹細胞を規定された細胞系譜へとプログラムする方法の開拓にも先駆的に取り組んだ。マウス ES 細胞では、単一のマスター転写因子(例えば Myod1、Hnf4a、Sfpi1、Ascl1)を一過性に過剰発現させることにより、筋細胞、肝細胞、血液細胞、神経細胞への直接的な分化誘導が可能であることを示した(2013年)。
さらに、エピジェネティック・プライミング(JMJD3c をコードする mRNA の導入)と MYOD1 をコードする mRNA を組み合わせることにより、ヒト ES/iPS 細胞から筋系細胞への分化変換効率を著しく向上させた(2016年、2017年a、2018年a)。また、体系的な転写因子相関マトリクスを用いることにより、ヒト ES/iPS 細胞を涙腺上皮(2017年b)、膵内分泌細胞(2018年b)、腎オルガノイド(2019年)、ドパミン作動性ニューロン(2020年)へ効率よく分化誘導する系譜特異的転写因子を同定した。加えて、合成 mRNA カクテル(例えば NGN1、NGN2、NGN3、ND1、ND2)を用いることで、機能的な神経細胞を10日以内に迅速に作製できることも示した(2017年c)。特筆すべきことに、NGN3 単独でも強力な神経誘導活性を有することを明らかにした(2017年d)。
これらの研究により、迅速性、拡張性、ならびに臨床応用可能性を兼ね備えた、フットプリントを残さない汎用的な細胞分化誘導プラットフォームが確立された。
Key References:
• Yamamizu et al. (2013). Identification of transcription factors for lineage-specific ESC differentiation.
https://pubmed.ncbi.nlm.nih.gov/24371809/
• Akiyama et al. (2016). Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/27802135/
• Akiyama et al. (2017a). Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells.
https://pubmed.ncbi.nlm.nih.gov/28491098/
• Hirayama et al. (2017b). Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells.
https://pubmed.ncbi.nlm.nih.gov/28649419/
• Goparaju et al. (2017c). Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/28205555/
• Matsushita et al. (2017d). Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors.
https://pubmed.ncbi.nlm.nih.gov/28610919/
• Akiyama et al. (2018a). Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing.
https://pubmed.ncbi.nlm.nih.gov/29352121/
• Ida et al. (2018b). Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/30359326/
• Hiratsuka et al. (2019). Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors.
https://pubmed.ncbi.nlm.nih.gov/30696889/
• Akiyama et al. (2020). Synthetic mRNA-based differentiation method enables early detection of Parkinson’s phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/33342090/
● T細胞ワクチンとしての制御可能自己複製RNA(c-srRNA)ベクター(2022年〜)
私の研究室は、温度制御型の自己複製RNA(controllable self-replicating RNA: c-srRNA)ベクターを開発し、これを脂質ナノ粒子を用いずに皮内投与するワクチンとして応用した(2023年a)。本ベクターは、皮膚温度(30〜35℃)では複製し、深部体温(37℃)では不活化されるよう最適化されており、タンパク質ブーストを行わない限り抗体産生はほとんど誘導しない一方で、CD4⁺およびCD8⁺T細胞応答を誘導することを示した。したがって、本ワクチンはT細胞ワクチンとして機能し、多様な変異病原体に対するワクチンとして応用できる可能性を有している。
さらに、私たちは SARS-CoV-2 の RBD をコードする c-srRNA ベクター(EXG-5003)を開発し、健常成人を対象とした二重盲検プラセボ対照第I/II相試験を実施した(2023年b)。その結果、本ワクチンは安全性を示し、単独投与では液性免疫応答をほとんど誘導しない一方で、細胞性免疫を誘導することが確認された。また、その後に承認済み mRNA ワクチンを接種した場合には、T細胞応答および抗体応答が増強されることが示された(2023年b)。
Key References:
• Amano et al. (2023a). Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity.
https://pubmed.ncbi.nlm.nih.gov/36968065/
• Koseki et al. (2023b). A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2.
https://pubmed.ncbi.nlm.nih.gov/38140172/
● ZSCAN4 の発見とその機能解析(2007年〜)
この研究は、私たちが1990年代初頭に開始した「マウス全遺伝子カタログ・プロジェクト」に端を発しており、初期胚、生殖系細胞、および幹細胞に関する包括的な遺伝子発現プロファイルに基づくものであった(2000、2003、2004年)。私たちは、接合子ゲノム活性化の過程で特異的かつ一過性に発現する遺伝子を探索し、2000年代初頭に、マウス2細胞期胚に特異的に発現する遺伝子としてZscan4を同定した(2007a)。さらに、マウスES細胞におけるZscan4の発現パターンを whole-mount mRNA in situ hybridization により調べたところ、Zscan4 は強く発現しているものの、任意の時点では細胞全体の 1〜5% にしか認められないことを見いだした(2007年a、2007年b)。この予想外の結果は、私がかつて研究していた「確率的遺伝子発現」における発現様式を想起させるものであった。このことを契機として Zscan4 のさらなる解析を進めたが、その後、Zscan4 の発現は確率的事象ではないことが明らかとなった。私たちは、Zscan4がテロメア伸長(2010年)、ゲノム安定性(2010年)、核型安定性(2015a)、DNAメチル化(2015b)、およびエピゲノム制御(2015b)において重要な役割を果たすことを明らかにした。これらのZSCAN4に関する基礎研究に基づき、Elixirgen Therapeutics社における私たちのチームは、骨髄不全を伴うテロメア病(TBDs)に対する細胞・遺伝子治療であるEXG34217を開発し、治験を進めている(https://clinicaltrials.gov/study/NCT04211714)。最初に治療された二人の患者の初期結果は NEJM Evidence に掲載された(2025年)。
• ZSCAN4 は哺乳類特異的な遺伝子であり、1個の SCAN ドメインと4個の zinc finger ドメインをコードする(2007年a)。
• マウスでは、Zscan4 の発現は着床前胚の2細胞期に限定されている。この一過性発現を抑制しても、あるいは持続させても、発生停止や異常が生じる(2007年a)。
• マウス ES 細胞では、ZSCAN4 の発現は一過性であり、持続時間は数時間にすぎない。任意の時点では、未分化 ES 細胞のうち 1〜5% のみが ZSCAN4 陽性である(2007年a)。しかしながら、約9継代の後には、ほぼすべての細胞が一度は ZSCAN4 陽性状態を経過することが示された(2010年)。
• ZSCAN4 陽性状態への移行は、複数の一過性現象を引き起こす。すなわち、相同組換えによる急速なテロメア伸長、2細胞期特異的遺伝子群の誘導、タンパク質合成の一時的な全般抑制、さらに減数分裂特異的遺伝子群の活性化である(2010年)。
• ES 細胞が ZSCAN4 陽性状態へ移行できないようにすると、約6継代後から増殖能が徐々に低下し、最終的には培養クライシスに至る。この段階では、大部分の細胞が異常核型を示し、一過性の ZSCAN4 活性化がゲノム安定性の維持に必須であることが示された(2010年)。
• 外因性 ZSCAN4 を強制的かつ一過性に誘導すると、ES 細胞は品質を損なうことなく通常よりはるかに長期間培養維持できることが示され、適切に制御された ZSCAN4 発現が幹細胞機能の維持と若返りの両方に寄与しうることが示唆された(2013年a)。
• 人工多能性幹細胞(iPS 細胞)の樹立過程に ZSCAN4 を組み込むことにより、iPS 細胞の品質が著しく向上することを示した(2012年)。
• ヒト膵臓では、ZSCAN4 が少数の推定幹細胞集団に強く発現しており、マウス以外においても保存された機能を有する可能性が示唆された(2013年c)。
• ZSCAN4 遺伝子の強制発現により、マウス ES 細胞、ダウン症候群患者由来初代線維芽細胞、およびエドワーズ症候群患者由来初代線維芽細胞において、染色体異常の修復の可能性が示された(2015年a)。
• また、マウス ES 細胞で ZSCAN4 が発現すると、エピゲノムに一過性かつ動的な変化が起こることも明らかにした。すなわち、クロマチン、特にヘテロクロマチンにおいて脱抑制と再抑制が生じ、テロメア、セントロメア周辺領域、その他の領域に由来する RNA が一過性に発現し、さらに核小体周辺にヘテロクロマチンが凝縮する現象も観察された(2015年b、2024年)。
• 雌雄いずれのマウスにおいても、Zscan4 は減数分裂期に特異的に発現することが見いだされた。減数第一分裂の pachytene 期および diplotene 期に特異的に発現する遺伝子は、それまで報告がなく、Zscan4 はその最初の例となった(2016年c)。
• Zscan4 は恒常的に発現する遺伝子ではなく、間欠的にのみ出現することから、ゲノム安定性の維持やテロメア伸長は連続的な過程ではなく、散発的に生じる現象であると考えられる。このことは、Zscan4 が極めて特異な「細胞若返り」機能を担っている可能性を示唆している。
• 私たちは、骨髄不全を伴うテロメア病患者を対象として、EXG34217のfirst-in-human第I/II相試験を実施した。EXG34217は、ZSCAN4をコードする温度感受性センダイウイルスベクターにより ex vivo で一過性に処理した自己CD34陽性造血幹細胞製品である。患者2例において、造血幹細胞の動員、アフェレーシス、および細胞治験薬投与が成功裏に行われた。治療を受けた両患者において、ex vivo でテロメア延長が認められ、その後 in vivo においても、より長いテロメアを有する末梢血細胞集団の出現が確認された。好中球数は改善し、1例では治療前に必要であったG-CSF投与が不要となった。投与後の安全性上の問題は認められなかった(2025年)。
Key References:
• Ko et al. (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.
https://pubmed.ncbi.nlm.nih.gov/10725249/
• Carter et al. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.
https://pubmed.ncbi.nlm.nih.gov/12727912/
• Hamatani et al. (2004). Dynamics of global gene expression changes during mouse preimplantation development.
https://pubmed.ncbi.nlm.nih.gov/14723852/
• Falco et al. (2007a). Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/17553482/
• Carter et al. (2007b). An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells.
https://pubmed.ncbi.nlm.nih.gov/18178135/
• Zalzman et al. (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells.
https://pubmed.ncbi.nlm.nih.gov/20336070/
• Hirata et al. (2012). Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells.
https://pubmed.ncbi.nlm.nih.gov/22355722/
• Amano et al. (2013a). Zscan4 restores the developmental potency of embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/23739662/
• Hung et al. (2013b). Repression of global protein synthesis by eif1a-like genes that are expressed specifically in the two-cell embryos and the transient zscan4-positive state of embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/23649898/
• Ko et al. (2013c). Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas.
https://pubmed.ncbi.nlm.nih.gov/23599043/
• Amano et al. (2015a). Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures.
https://pubmed.ncbi.nlm.nih.gov/26324424/
• Akiyama et al. (2015b). Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
https://pubmed.ncbi.nlm.nih.gov/26324425/
• Ko (2016a). Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4.
https://pubmed.ncbi.nlm.nih.gov/27475850/
• Sharova et al. (2016b). Emergence of undifferentiated colonies from mouse embryonic stem cells undergoing differentiation by retinoic acid treatment.
https://pubmed.ncbi.nlm.nih.gov/27130680/
• Ishiguro et al. (2016c). Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis.
https://pubmed.ncbi.nlm.nih.gov/27699653/
• Ishiguro et al. (2016d) Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos.
https://pubmed.ncbi.nlm.nih.gov/27699651/
• Akiyama et al. (2024). ZSCAN4-binding motif-TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes.
https://pubmed.ncbi.nlm.nih.gov/38153767/
• Myers et al. (2025). Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.
https://pubmed.ncbi.nlm.nih.gov/39998303/
■ FULL BIOGRAPHY OF Minoru S.H. Ko, M.D., Ph.D.
● CURRENT POSITION
• Chief Scientific Officer, Elixirgen Therapeutics, Inc.
• Professor Emeritus, Keio University
● EDUCATION
• Keio University School of Medicine, Tokyo, Japan (M.D., 1986)
• Keio University School of Medicine, Tokyo, Japan (Ph.D., 1991; Advisor Dr. Toshiya Takano)
● PROFESSIONAL APPOINTMENTS
1988-1991 Researcher, Furusawa MorphoGene Project, ERATO, JST, Tsukuba, Japan
1991-1992 Group Leader, Furusawa MorphoGene Project, ERATO, JST, Tsukuba, Japan
1992-1996 Assistant Professor, Center for Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, Michigan
1996-1998 Associate Professor (Tenured), Center for Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, Michigan
1998-2011 Senior Investigator (Tenured), Chief of Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland
2012–2016 Special Volunteer, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland
2012- Co-founder and Chief Scientific Officer, Elixirgen, LLC, Baltimore, Maryland
2012-2022 Professor and Chair, Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan
2016-2025 Founder and Chief Scientific Officer, Elixirgen Scientific, Inc. (now Ricoh Biosciences, Inc.), Baltimore, Maryland
2017- Co-founder and Chief Scientific Officer, Elixirgen Therapeutics, Inc., Baltimore, Maryland
2022- Professor Emeritus, Keio University School of Medicine, Tokyo, Japan
● OTHER PROFESSIONAL APPOINTMENTS
1988-1992 Adjunct Instructor, Department of Microbiology, Keio University School of Medicine, Tokyo, Japan
1996-1998 Group Leader, Genome Asymmetry Group, ERATO Doi Bioasymmetry Project, JST, at Wayne State University School of Medicine, Detroit, MI
1999-2004 Project Officer, DNA sequencing contract to PE-Applied Biosystems: mouse cDNA project, NIH
1998-2007 Project Officer, UNISYS Informatics Support for large-scale sequencing project, NIH
2001-2008 Principal Investigator, CRADA with Agilent Technologies: Design and development of mouse DNA microarrays, NIH
2004-2011 Co-leader, NIH Stem Cell Interest Group
2012-2016 Special Volunteer, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD
2013–2015 Research Leader, MEXT Center of Innovation Program (COI-STREAM) trial, “Center for System Medicine to Create the Global Standard for Healthy Longevity” at Keio University, Tokyo, Japan
2013–2015 Vice Dean, Keio University School of Medicine, Tokyo, Japan
2015-2015 Director, Centenarian Research Center, Keio University School of Medicine
2015–2017 Director, Keio University Leading Research Center for System Medicine Research and Development
2017–2021 Director, Keio University Leading Research Center for Medical AI
● HONORS AND AWARDS
2001 NIH Merit Award
2009 NIA Director’s Award
2011 NIH Director’s Award
● LICENSURE AND BOARD CERTIFICATION
National License for Medical Practice, Japan, 1986
● STUDY SECTIONS/REVIEW COMMITTEES (EXAMPLES)
1993 Department of Energy (DOE) Review Panel on US Human Genome Program
1996 National Science Foundation (NSF) Review Panel for the RFA on Human Genome Diversity
1997 National Institutes of Health (NIH) Genome Study Section
1999 National Institutes of Health (NIH) Genome Study Section
1999 Department of Energy (DOE) Review Panel on US Human Genome Program
2000 National Institute on Aging (NIH), Review Panel for the High Throughput Technology Supplemental Requests
2004 Review Panel for the research program of Oakridge National Laboratory, DOE
2004 Review Panel for the grant proposal to Navy Research Program, DOD
2004 Reviewer for a grant proposal to March of Dimes Birth Defects Foundation.
2004 Reviewer, NSF CAREER Proposal
2004 Reviewer, NIH JSPS Fellowship Review Committee
2005 Reviewer, NIH JSPS Fellowship Review Committee
2005 Reviewer, NSF Grant Proposal
2005 Reviewer, NSF Grant Proposal
2006 Reviewer, NSF Grant Proposal
2006 Reviewer, NIH Graduate Students Festivals
2007 Reviewer, NIH JSPS Fellowship Review Committee
2007 Reviewer, NSF CAREER Proposal
2008 Reviewer, NIH JSPS Fellowship Review Committee
(Omitted after 2008))
● ADVISORY BOARDS (EXAMPLES)
1994 Member, Advisory Board, Experimental Evolution Workshop, ERATO, JST, Tokyo, Japan.
1995 Member, National Science Foundation (NSF) Advisory Panel on Human Genome Diversity
2005 Scientific Advisory Board for Bovine Embryo Transcriptome Analysis (BETA) Project,
Canadian Genome Initiative, Canada (Invited, but declined due to NIH regulation)
2005-2008 Advisory Board, The Jackson Laboratory, Mouse Genome Database (MGD), USA
2006-2009 Advisory Board, The Jackson Laboratory, Gene Expression Database (GXD), USA
2006 Discussant, Round table discussion on Developmental Biology and Stem Cells,
Nature Publishing Group
2014–2018 Special Advisor (Member, Research Strategy Council, Office of the President), RIKEN, Japan
2014– Member, Research Advisory Committee, Central Institute for Experimental Animals (CIEA), now called Central Institute for Experimental Medicine and Life Sciences (CIEM), Kawasaki, Japan
2017–2019 Member, External Expert Committee, RIKEN Program for Promotion of the Medical Science Innovation Hub
● GRANT PROPOSAL REVIEW (EXAMPLES)
2007 Wellcome Trust Grant Review: Stem Cell Biology
2007 Canada Research Chair Review: Stem Cell Biology
2007 AFM Research Grant Review: Stem Cell Biology
(Omitted after 2008)
● SESSION CHAIR (EXAMPLES)
2001 Co-Chair, NH Research Festival, Minisymposium “Mouse Embryogenomics: Frontiers of Developmental Biology and Genomics”
● LABORATORY MEMBERS AT WAYNE STATE UNIVERSITY, DETROIT, MICHIGAN (1992-1998)
Postdoctoral Fellows
1993-1993 Satoshi Matsuda, M.D./Ph.D.
1993-1993 Shigeru Masamura, M.D./Ph.D.
1994-1994 Nanding Zhao, Ph.D.
1995-1996 Yushun Cui, Ph.D.
1995-1997 Shinichi Yotsumoto, M.D./Ph.D.
1995-1997 Hiroyuki Fujiwara, Ph.D.
1995-1997 Hiroshi Nakashima, M.D./Ph.D.
1995-1997 Hiroshi Harada, M.D.
1996-1997 Wei Xue, M.D./Ph.D.
1996-1998 John Kitchen, Ph.D.
1997-1998 Tokihiko Shimada, M.D./Ph.D.
1996-1998 Rhonda H. Nicholson, Ph.D.
Research Assistant/Technical Staff
1992-1995 Joseph H. Horton, B.S.
1992-1997 Xueqian Wang, M.D.
1995-1995 Cheryl Moore, B.S.
1995-1995 Rene Salyer, B.S.
1995-1995 Ted Scancella, B.S.
1995-1996 Eric Pryor, B.S.
1995-1996 Jason Paris, B.S.
1995-1997 Jeannine Wells-Smith, B.S.
1995-1998 Tracy A. Threat, B.S.
1995-1998 Xiaohong Wang, M.S.
1996-1997 Shiho Fukui, B.A.
1996-1998 Sonja Davis, B.P.A.
1997-1998 Tong Sun, M.S.
1997-1998 Erico Yogo, B.A.
1997-1998 Yuling Liang, B.S.
1996-1997 Scott P. Mason, B.S.
1996-1998 Meng K. Lim, B.S.
1996-1998 Marija J. Grahovac, B.S.
1996-1997 Maged K. Rizk, B.S.
1997-1997 Paul Paonessa, B.S.
1995-1996 Jason Yoas, B.S.
1996-1997 Sundip S. Patel, B.S.
Student Assistant (IT Computational work)
1993-1994 Srinivas Inaganti, B.S.
1994-1995 Ramachandra Kakulawaram, B.S.
1994-1995 Sridhar Reddy Andapally, B.S.
1995-1996 Jeevan Nalamada, B.S.
1995-1996 Rajiv Muthyala, B.S.
1996-1997 Sunil Kosuru, B.S.
1996-1997 Sudheer Tummula, B.S.
Graduate Student, Rotation
1994 Michail Kolonin, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine
1994 Chongsuk Ryou, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine
1994 Kirk Yousif, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine
1996 Sompong Vongpunsawad, Center for Molecular Medicine and Genetics, Wayne State University school of Medicine
High School Student Intern
1993-1994 Jing Qian, Cass Tech High School.
1994-1995 Carla Ellison, Cass Tech High School.
1995-1996 Dia Hodnett, Cass Tech High School.
● LABORATORY MEMBERS AT NIA, NIH, BALTIMORE, MARYLAND (1998-2011)
Staff Scientist, Biologists, and Technical Staff
2003-2011 Alexei A. Sharov, Ph.D.
2003-2011 Lioudmila Sharova, Ph.D.
2009-2011 Misa Amano, M.S.
2009-2011 Hong Yu, B.S.
1998-2011 Yulan Piao, M.D.
1999-2011 Carole Stagg, B.S.
2002-2010 Uwem Bassey, B.S.
2005-2006 Eric Douglas
1998-2000 Meng K. Lim, M.S.
1999-1999 Tammy Stockette, M.S.
1999-2001 Amber Luo, M.D.
2000-2002 Shirley Deng, M.S.
2001-2004 Patrick Martin, B.S.
2003-2005 Yuxia Wang, B.S.
Computer Specialists
1999-2011 Dawood Dudekula, B.S.
1999-2011 Yong Qian, M.S.
Postdoctoral Fellows
2010-2011 Tomohiko Akiyama, Ph.D.
2008-2011 Hsih-Te Yang, Ph.D.
2011-2011 Sandy Hung, Ph.D.
2011-2011 Raymond Wong, Ph.D.
2008-2011 Yuhki Nakatake, Ph.D.
2009-2011 Tomokazu Amano, Ph.D.
2007-2011 Michal Zalzman, Ph.D.
2009-2011 Tetsuya Hirata, M.D., Ph.D.
2008-2010 Akira Nishiyama, Ph.D.
2008-2011 Li Xin, M.D., Ph.D.
2009-2011 Lina S. Correa-Cerro, M.D., Ph.D.
2009-2010 Manxiang Li, Ph.D.
2007-2010 Manuela Monti, Ph.D.
2005- 2008 Ilaria Stanghellini, Ph.D.
2005-2005 Wakako Hashimoto, M.D.
2003-2006 Ryo Matoba, Ph.D.
2004-2007 Sung-Lim Lee, D.V.M., Ph.D.
2002-2006 Vincent VanBuren, Ph.D.
2002-2007 Geppino Falco, Ph.D.
2000-2006 Wendy L. Kimber, Ph.D.
2000-2006 Mark G. Carter, Ph.D.
2000-2006 Kazuhiro Aiba, Ph.D.
2001-2004 Toshiyuki Yoshikawa, M.D., Ph.D.
2001-2004 Toshio Hamatani, M.D., Ph.D.
2001-2001 Hiroshi Suemizu, Ph.D.
2000-2000 Maria Granovsky, Ph.D.
1998-2000 Serafino Pantano, Ph.D.
1998-2000 Yuri Sano, M.D., Ph.D.
1998-2003 Tetsuya Tanaka, Ph.D.
1999-2002 Saied Jaradat, Ph.D.
Post baccalaureate Fellows
1998-1999 Marija J. Grahovac, M.S.
1998-2001 George Kargul, M.S.
2008-2009 Marshall Thomas
2008-2009 Gregory Mowrer
2008-2009 Emily Meyers
2008-2009 Samir Mehta
2008-2009 Sarah Yee
2009-2011 Hien Hoang
2009-2009 Eugene Kim
2009-2010 Richard Tapnio
2009-2011 Bernard Y. Binder
2010-2011 Justin Malinou
2010-2011 Sarah Sheer
2010-2011 Jean S. Cadet
Summer Students:
1999 Anastasia Kolendo
2000 Roman Johnson
2001 Brian Everist
2002 Lawrence David
2002, 2003 Arpun Nagaraja
2003 Lauren Wilson
2003, 2004 Ajish George
2005 Tara Howard
Visiting Students:
2004 Maud Vallee, Ph.D. candidate
2005 Nina Rogers, Ph.D. candidate
● LABORATORY MEMBERS AT DEPARTMENT OF SYSTEMS MEDICINE, KEIO UNIVERSITY SCHOOL OF MEDICINE, TOKYO (2012-2022)
2012-2022 Shigeru Ko, M.D., Ph.D. (Associate Professor/Project Professor)
2012-2020 Yuki Nakatake, Ph.D. (Assistant Professor)
2012-2019 Nana Chikazawa, M.S. (Project Researcher)
2012-2018 Mayumi Oda, Ph.D. (Assistant Professor)
2012-2022 Norio Goda, Ph.D. (Project Assistant Professor)
2012-2012 Go Nagamatsu, Ph.D. (Assistant Professor)
2012-2012 Yuko Isono (Office Manager)
2012-2015 Masatoshi Hirayama, M.D. (Visiting Ph.D. Graduate Student)
2012-2014 Tomoo Ueno (Technical Staff)
2012-2014 Emi Tsutsui (Office Manager)
2012-2016 Miki Sakota (Project Researcher)
2012-2014 Naoko Fujita (Technical Staff)
2013-2018 Shunichi Wakabayashi (Project Researcher)
2013-2022 Tomohiko Akiyama, Ph.D. (Assistant Professor)
2013-2021 Saeko Sato (Project Researcher)
2013-2014 Kenta Tsutsui, M.D., Ph.D. (Collaborative Researcher)
2013-2016 Atsushi Hiroike, Ph.D. (Project Lecturer)
2013-2014 Naoto Akira (Collaborative Researcher)
2013-2015 Lars Martin Jakt, Ph. D. (Project Lecturer)
2013-2015 Siu Shan Mak, Ph.D. (Project Assistant Professor)
2013-2016 Miyako Murakami (Project Researcher)
2013-2015 Shih Te Yang, Ph.D. (Visiting Assistant Professor)
2013-2015 Fumi Higashimura (Office Manager)
2013-2018 Sravan Kumar Goparaju, Ph.D. (Project Assistant Professor)
2013-2014 Kara Besher (Office Manager)
2013-2014 Maiko Mori (Office Manager)
2014-2018 Ken Hiratsuka, M.D. (Visiting Ph.D. Graduate Student)
2014-2018 Misako Matsushita, M.D. (Visiting Ph.D. Graduate Student)
2014-2022 Yoko Tauchi (Office Manager)
2014-2019 Mayumi Ikeda (Office Manager)
2014-2016 Ayano Murase (Office Manager)
2014-2019 Hiromi Kimura (Project Researcher)
2014-2019 Kei-ichiro Ishiguro, Ph.D. (Project Associate Professor)
2014-2016 Atsumi Soma, Ph.D. (Project Faculty)
2014-2016 Chiaki Okura (Project Researcher)
2014-2016 Ryo Matoba, Ph.D. (Project Lecturer)
2015-2015 Yuki Aoki, M.D. (Collaborative Researcher)
2015-2017 Hideomi Ida, M.D. (Collaborative Researcher)
2015-2017 Yann Tapponier, Ph.D. (Postdoc Fellow)
2015-2015 Jun Tanigawa, Ph.D. (Collaborative Researcher)
2016-2016 Kazuto Katsuse, M.D. (Ph.D. Graduate Student)
2016-2018 Hanaka Saito (MS Graduate Student)
2020-2022 Toshiya Nakahara (MS Graduate Student)
● PRESENTATIONS (examples)
Invited international or national meetings
1992 Taniguchi International Symposium entitled "cDNA Research Today," Osaka, Japan. Towards a mouse whole cDNA catalog.
1992 Winter Conference of Korean Association of Molecular Biology, Suanbo, Republic Korea. Towards a mouse whole cDNA catalog.
1992 The 7th Molossinus Symposium, Takasaki, Japan. Mouse whole cDNA catalog and its application for gene mapping.
1992 2nd International Workshop on the identification of Transcribed Sequences, San Francisco. The 3'-end region of cDNAs as PCR-based polymorphic markers for an expression map of the mouse genome.
1995 Human Gene Map Workshop II, Banbury Center, Cold Spring Harbor Laboratory
1995 Panelist, Panel discussion for the mouse EST project, The 9th International Mouse Genome Conference, Ann Arbor, Michigan
1996 The 4th JRDC International Symposium, Experimental Approaches to the Evolutionary Biology, Tokyo, Japan
1997 The Tenth International Workshop organized by the International Institute of Genetics and Biophysics, CNR Naples, Italy. Title: Genome-based analysis of gene regulation and its evolution”
1999 The Jackson Laboratory Symposium (June 30- July 3, 1999), "Mouse Initiatives: Advanced Functional Genomics," Bar Harbor, Maine, USA. Developmental Genomic Approach to Mouse Embryology.
2000 International Symposium “Topics from Human Genome Project” (January 17-January 18, 2000), Tokyo, Japan. Developmental Genomic Approach to Mouse Embryology.
2000 ERATO Doi Bioasymmetry Project Symposium (September 6, 2000), Makuhari, Chiba, Japan.
2000 The 3rd International Workshop on Advanced Genomics (Nov 13 - 14, 2000), Yokohama, Japan.
2001 Schering Minisymposium “Molecular Mechanisms of Implantation”, Berlin, Germany. February 2nd , 2001.
2001 Keystone Symposium “Pluripotent Stem Cells: Biology and Applications (C1)” Durango, Colorado. Feb 6 - Feb 11, 2001.
2001 The Sixth Annual Mayo-Luther Forum on Hematopoietic Stem Cells, Mayo Clinic, Rochester, Minnesota, June 15, 2001.
2001 NIH Research Festival, Minisymposium “Mouse Embryogenomics: Frontiers of Developmental Biology and Genomics,” Maryland, October 3, 2001.
2001 International Symposium on Stem Cells and Therapeutic Cloning, Seoul, Korea. November 25, 2001.
2002 The 2nd International Symposium: Frontiers in Pancreatic Research, Nagoya, Japan. March 30-April 1.
2002 International Workshop on embryo genomics in farm animals. July 19 (In conjunction with the American Association of Animal Science Meeting July 21-24), Quebec, Canada.
2002 Serono Symposia International conference on “Genesis and Fate of the Preimplantation Embryo”, September 29-October 1, 2002 in Sorrento, Italy.
2003 Human Genome Meeting (HGM) 2003, Plenary Session on, 'Stem Cell Genomics', Cancun, Mexico, April 27-30, 2003.
2003 Serono Foundation, Workshop on Human Implantation Devoted to Genomics/Proteomics Discovery of The Reproductive Tract In Health And Disease. Madrid, Spain, June 28, 2003.
2004 International Embryo Transfer Society Annual Conference, Portland, Oregon, USA, January 11-13.
2004 Society for Gynecologic Investigation, Annual Meeting, Houston, Texas, March, 2004.
2004 PRICPS2004, the 1st Pacific-Rim International Conference on Protein Science, Yokohama, Japan, April 14-18,2004.
2004 Gordon Research Conference on Reproductive Tract Biology. Connecticut College in New London, Connecticut. June 6-11, 2004.
2004 Cold Spring Harbor Laboratory Course. Molecular Embryology of the Mouse. June 9-29, 2004. Lecture on Microarrays and Early Development.
2004 International Symposium at The Royal Society 6-9 Carlton House Terrace, London, SW1Y 5AG, September 30 – October 1, 2004: MORAL, LEGAL, AND SOCIAL IMPLICATIONS OF REPRODUCTIVE TECHNOLOGY.
2004 S.I.S.M.E.R. forum: Genesis of Life, Bologna, Italy. Sep 11, 2004.
2005 The Sixth International Symposium on Preimplantation Genetics. Queen Elizabeth II Conference Centre, London, UK: 19-22 May 2005.
2005 International Stem Cell Symposium, Kyoto, Japan, November.
2005 The 2nd Annual Meeting for the Korean Society of Animal Reproduction. Oct 26-27, Seoul, Korea (Invited, but declined due to schedule conflict)
2006 2nd International Symposium on Animal Functional Genomics (2nd ISAFG) on May 16-19, 2006. Michigan State University, East Lansing, Michigan, USA (Invited, but declined due to NIH regulation).
2006 "New Insights and Perspectives in Stem Cell Research", International Symposium to cerebrate 100th year of Camillo Golgi’s Nobel Prize. University of Pavia, Pavia, Italy. May 16th - 17th, 2006.
2006 Tecnobios Procreazione Symposium 2006 and 2nd International Conference on the Cryopreservation of the Human Oocyte. Bologna, Italy. October 5-7, 2006.
2006 6th International Symposium on Developmental Biotechnology, October 27, 2006. Seoul, South Korea.
2006 16th Lake Shirakaba Conference, The Caribbean Islands, Grenada, December 6-7, 2006. Invited, but declined due to the schedule conflict.
2007 The fifth annual CDB Symposium "Germ Line versus Soma: Towards Generating Totipotency", RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. March 26-28, 2007.
2007 34th Annual National Conference of the Association of Clinical Biochemists of India, Delhi, India, 18th-20th December, 2007. Invited, but declined due to the schedule conflict.
2007 Reproductive Biology Course, Woods Hole Marine Biological Laboratory, MA
2007 40th Annual Meeting of the Society for the Study of Reproduction, San Antonio, Texas, July 22-25.
2007 17th Lake Shirakaba Conference, Vedbaek, Denmark, October 29-31.
2007 Symposium on Germ Cell Development, Reprogramming, and Epigenetics Tokyo, Japan. November 21 and 22.
2008 Stem Cell Symposium (Memorial Symposium for late Anne McLaren). Pavia, Italy, January 2008. Invited, but declined due to the conflict of schedule.
2008 Mini symposium for Preimplantation Development, Temple University, PA. August 15-16. Invited, but declined due to the conflict of schedule.
2008 Reproductive Biology Course, Woods Hole Marine Biological Laboratory, MA
2009 Pre-congress Course entitled "From Gamete to Heartbeat: the missing link" at the 2009 ESHRE Annual Meeting in Amsterdam, 28 June 2009. Invited, but declined due to the conflict of schedule.
2009 Keystone Symposium Preimplantation Embryos, invited, but declined due to the conflict of schedule.
2009 NIH Research Festival, Stem Cell Biology, Bethesda, MD.
2009 Plenary Lecture, Japanese Ova Society, Tokyo, Japan.
2009 Systems Biology of Human Aging Symposium, Baltimore, MD.
2010 Systems Biology of Stem Cells, UC, Irvine, invited, but declined due to the conflict of schedule.
2010 Abreu Memorial Keynote Address at the National Student Research Forum (NSRF). University of Texas Medical Branch, Galveston, TX, invited, but declined due to the conflict of schedule
2010 JSPS/JHU/NIA Symposium Aging vs. Regenerative Medicine: How Much Can Stem Cells Do? Baltimore, MD
2011 Scottish Stem Cell Network Symposium, “Mechanisms of Lineage Specification,” Edinburgh, UK
2011 BIO 2011 Convention, Washington, D.C.
2011 The ninth annual CDB Symposium "Epigenetic Landscape in Development and Disease", RIKEN Center for Developmental Biology (CDB) in Kobe, Japan.
2011 KEY Forum in Developmental Biology and Regenerative Medicine, Kumamoto University, Kumamoto, Japan
2011 SENS Foundation 5th Symposium, Queens’ College, Cambridge, UK
2011 Serono Symposia International Foundation Conference on: Individualized controlled ovarian stimulation and objective gametes and embryo selection, Yokohama, Japan
2012 How do ES cells maintain their exceptional genome stability? Baltimore Area Repair Symposium (BARS), Baltimore, Maryland, USA
2012 Recapitulating embryonic program: Reactivation of early embryonic genes by Zscan4 during the generation of iPSCs. Invited lecture. 11th Congress of the Japanese Society for Regenerative Medicine, Yokohama, Japan.
2012 What ES cells can teach us about immortality and rejuvenation. Symposium, Japanese Society of Anti-Aging Medicine, Tokyo, Japan.
2013 Mechanisms for maintaining genome stability in embryonic stem cells. Annual Meeting of the Epigenome Research Society, Nara, Japan.
2013 Current status and future prospects of systems medicine. Toward the Realization of Personalized Medicine—Perspectives from companion diagnostics, preventive medicine, and systems medicine. BioJapan 2013 Symposium, Yokohama, Japan.
2013 How do ES cells maintain their exceptional genome stability? NIEHS Symposium on Unlocking the Promise of Stem Cells. National Institute of Environmental Health Sciences, National Institutes of Health. Durham, North Carolina, USA.
2013 Cellular aging and rejuvenation learned from stem cells. 6th Forum, International Medical Science Research Society, Tokyo, Japan.
2013 Stem cell gene networks. Osaka University Symposium on Mathematical Sciences, Osaka, Japan.
2013 Mechanisms for maintaining genome stability in embryonic stem cells. Symposium, Annual Meeting of the Molecular Biology Society of Japan, Kobe, Japan.
2013 Stem cell gene networks. Annual Meeting of the Japan Society for Industrial and Applied Mathematics, Fukuoka, Japan.
2013 Controlling cell differentiation through understanding gene regulatory networks. Symposium, “Current Status of Developmental and Regenerative Research Using Systems Biology Approaches,” 86th Annual Meeting of the Japanese Biochemical Society, Yokohama, Japan.
2014 Preimplantation embryos and systems medicine. 32nd Annual Meeting of the Japan Society of Fertilization and Implantation. Invited lecture. Tokyo, Japan.
2015 Systematic Analyses of Transcription Factor Networks in Mouse and Human Pluripotent Stem Cells; Zscan4: transient remodeling and transcription of heterochromatin in mESCs. Systems Biology of Stem Cells: SyBoSS Double Conference, Oberstdorf, Germany.
2015 Mechanisms for genome stabilization in pluripotent stem cells. Symposium, 14th Annual Meeting of the Japanese Society for Regenerative Medicine, Reprogramming and Pluripotent Stem Cells, Tokyo, Japan.
2015 Molecular mechanisms regulating the developmental potential of early embryos and pluripotent stem cells. 60th Annual Meeting of the Japan Society for Reproductive Medicine. Invited lecture. Yokohama, Japan.
2017 38th Annual Meeting of the Japanese Society of Inflammation and Regeneration, “Disease and Stem Cells,” Osaka, Japan
2018 KEY FORUM: “Stem Cell Traits and Developmental Systems,” Kumamoto, Japan
2018 Japanese Society for Medical Mycology, “Systems Medicine and Future Medicine”
2019 Symposium of the Japan Medical Association, Japan Medical Association Hall
2019 42nd Annual Meeting of the Molecular Biology Society of Japan, Fukuoka
2021 11th Joint Symposium on New Anticancer Drug Development + 5th NEXT Medical Device Development Symposium
2021 Link-J Symposium, “Frontiers of Drug Discovery”
Invited seminars or lectures (examples)
1991 Hamburg University, Hamburg, Germany. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1991 Pasteur Institute, Paris, France. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1991 NIH, Bethesda, MD. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1991 The Jackson Laboratory, Bar Harbor, ME. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1991 Wayne State University, MI. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1991 Lawrence Livermore National Laboratory, Livermore, CA. A whole mouse cDNA catalog: an equalized cDNA library by the reassociation of the short double-stranded cDNAs.
1993 University of Michigan, Ann Arbor, MI. Mouse biology with an equalized embryo cDNA library.
1995 Kresge Eye Institute, Wayne State University, Detroit, MI. Mouse biology with an equalized cDNA library.
1995 Washington University School of Medicine, St. Louis, MO: A whole genome approach for disease gene finding from human and mouse genome.
1996 Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan: Fetal placenta development and genomic imprinting.
1996 Keio University School of Medicine, Tokyo, Japan: Fetal placenta development and genomic imprinting.
1996 National Institute on Aging, National Institutes of Health, Baltimore, MD. Systematic analysis of genes expressed in the extra-embryonic tissues: Implications for gene clustering and genomic imprinting.
1997 Wayne State University, Department of Biological Sciences, Detroit, MI. Systematic analysis of genes expressed in the extra-embryonic tissues: Implications for gene clustering and genomic imprinting.
1997 Wayne State University, Center for Molecular Medicine and Genetics, Detroit, MI. A new genomics approach for developmental biology: Implantation as a model system.
1998 Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, Milwaukee, Wisconsin: A new genomics approach for developmental biology: Implantation as a model system.
1998 Wayne State University, C.S. Mott Center, Detroit, Michigan: A new genomics approach for developmental biology: Implantation as a model system
1999 Johns Hopkins University: Developmental Genomics Approach to Early Mouse Embryogenesis
2000 NICHD, NIH.
2000 Children’s Hospital of Washington, D.C.
2000 NIDCR, NIH
2000 Niigata University School of Medicine, Niigata, Japan
2000 Central Institute for Experimental Animals, Kawasaki, Japan.
2000 Carnegie Institute of Embryology, Baltimore, MD.
2001 NCI/NIH, Fredrick, MD.
2001 University of Louisville, Kentucky
2002 RIKEN Bio Resource Center, Tsukuba, Japan
2002 Washington University, St. Louis, MO
2003 Center for Genomic Regulation, Barcelona, Spain.
2004 NIH Microarray Workshop: May 12, 2004.
2004 NICHD/NIH, Bethesda, MD.
2004 Wayne State University, Detroit, Michigan, USA
2004 University of Pennsylvania, Center for Woman’s Health, Philadelphia, USA
2005 Roslin Institute, Roslin, UK
2005 Institute of Stem Cell Research (ISCR), University of Edinburgh, Edinburgh, UK
2006 Center of Regenerative Biology, University of Connecticut. CT.
2006 University of Missouri, Columbia, MO
2006 Center for Stem Cell Biology, Vanderbilt University, TN
2007 Johns Hopkins University, McKusick-Nathans Institute of Genetic Medicine, MD
2007 Carnegie Institute of Washington, Baltimore, MD
2010 NIH Scientific Directors Meeting, NIH, Bethesda, MD
2010 NIH Institute/Center Directors Meeting, NIH, Bethesda, MD
2010 Cornell University, NY
2011 City of Hope, Duarte, CA
2011 Keio University School of Medicine, Tokyo, Japan
2011 National Advisory Council on Aging, NIH, Bethesda, MD
2011 National Eye Institute (NEI), NIH, Plenary Lecture for Focus on Fellows (Annual Retreat for Postdoc Fellows), MD
2011 National Institute for Environmental Health Sciences (NIEHS), NIH, NC.
2012 Overview and Future Direction. Laboratory of Genetics, National Institute on Aging, National Institutes of Health. Baltimore, Maryland, USA.
2012 Connecting the dots: Reactivation of early embryonic genes during the generation of induced pluripotent stem cells. Office of Scientific Director’s seminar series. National Institute on Aging, NIH, Baltimore, Maryland, USA.
2012 Connecting the dots: Systems approaches to early embryos and stem cells. iCeMS Retreat, Kyoto University WPI Institute for Integrated Cell-Material Sciences, Osaka, Japan.
2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Shinanomachi Gut Forum, Tokyo, Japan.
2012 Controlling cell differentiation through understanding gene regulatory networks. Keio GCOE Final Symposium, Tokyo, Japan.
2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Department of Neurology Seminar, Keio University School of Medicine, Tokyo, Japan.
2012 What ES cells can teach us about immortality and rejuvenation. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
2012 What systems medicine aims to achieve. Symposium hosted by the Office for Promotion of Research Collaboration, Keio University: The Dawn of Systems Medicine—Toward New Collaboration among Medicine, Engineering, and Pharmacy, Tokyo, Japan.
2012 Systems biology of development and regenerative medicine. Special Lecture, Developmental Kidney Research Meeting, Tokyo, Japan.
2012 Analysis of gene networks by systems approaches and its application to stem cell engineering. Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
2012 Recapitulating the embryonic gene expression program: Reactivation of early embryonic genes by Zscan4 during iPSC generation. Seminar, National Center for Child Health and Development, Tokyo, Japan.
2012 Discovery of Zscan4 through a systems medicine approach and the future of regenerative medicine. Seminar, Shonan Research Center, Takeda Pharmaceutical Company, Tokyo, Japan.
2012 What ES cells can teach us about immortality and rejuvenation. 5th Tokyo Anti-Aging Academy, Tokyo, Japan.
2012 What systems medicine aims to achieve. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
2012 The future of increasingly globalized science: Insights gained from 20 years in the United States. Young Investigator Education Symposium, Molecular Biology Society of Japan, Fukuoka, Japan.
2012 Whole-Genome Gene Expression Profiles: Theory, Experiment, and Data Analysis. Special Lecture IV in Bioinformatics and Life Science, Tokyo Institute of Technology, Tokyo, Japan.
2013 Controlling cell differentiation through understanding gene regulatory networks. Lab Chief Lunch Seminar. National Institute on Aging, National Institutes of Health. Baltimore, Maryland, USA.
2013 Genetic and epigenetic hierarchies distinguishing pluripotent and trophoblast stem cells. Group presentation. JST-CIHR Joint Research Program on "Epigenetics of Stem Cells." Toronto, Canada.
2013 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. Agilent Genomics Forum, Tokyo, Japan.
2013 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. Metabolic Syndrome Research Meeting: Inter-Organ Networks and Vascular Biology, Tokyo, Japan.
2013 Systematic analysis of gene expression networks in pluripotent stem cells. BBSRC-JST UK-Japan Joint Program Meeting, Hokkaido, Japan.
2013 Systems medicine and medical innovation. CIO Research Group Annual Workshop, Medical Innovation Conference, Tokyo, Japan.
2013 Molecular mechanisms of early development, stem cells, and reprogramming. Open Seminar, Central Institute for Experimental Animals (CIEA), Kawasaki, Japan.
2013 Systems Medicine – Systems Medicine and Medical Care 30 Years from Now. Sixth-Year Case Review, Keio University School of Medicine, Tokyo, Japan.
2013 Cellular aging and rejuvenation learned from stem cells: Clinical applications of systems medicine. Kanto Clinical Dermatology Research Meeting, Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
2013 The future of biomedical science and medicine enabled by systems medicine. Seminar, Hitachi Central Research Laboratory, Tokyo, Japan.
2013 Cellular aging and rejuvenation learned from stem cells. 16th Kanto Heart Seminar, Tokyo, Japan.
2013 What the COI-T Center for System Medicine and Healthcare to Establish the Global Standard for Healthy Longevity aims to achieve. Innovation Brought by Systems Medicine and Healthcare to Establish the Global Standard for Healthy Longevity. Symposium hosted by Keio University, Tokyo, Japan.
2014 What the Center for System Medicine and Healthcare to Establish the Global Standard for Healthy Longevity aims to achieve. 94th Keio Medical Society General Meeting and Symposium, Tokyo, Japan.
2014 Toward Regenerative and Rejuvenative Medicine: Systematic Manipulation and Analysis of Pluripotent Stem Cells. 2nd IRG Meeting, Tokyo, Japan.
2014 Transcriptional regulatory networks involved in early development, stem cells, and reprogramming. 6th Signal Network Research Meeting, Tokyo, Japan.
2015 Can we learn “immortality” from ES cells? Mechanism of Germline Immortality. Summer Retreat of the Extramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
2015 Functions of ZSCAN4 and its therapeutic applications. Seminar, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.
2015 Toward Systems Medicine: Healthy Longevity and Systems Medicine. 4th Oda Memorial International Symposium, National Center for Global Health and Medicine, Tokyo, Japan.
2016 The ZSCAN4 gene responsible for genome stability in stem cells: Epigenomic regulatory mechanisms and their therapeutic applications. Seminar, National Center for Child Health and Development, Tokyo, Japan.
2016 What is Systems Medicine? Systematic Analyses of Transcription Factor Networks in Mouse and Human Pluripotent Stem Cells. Biology and Therapeutic Application of Zscan4. Keio Joint Summer Research Program, Tokyo, Japan.
2016 Genome Stability and Epigenomic Regulation in Stem Cells by ZSCAN4. Special Graduate Lecture, Tokyo Medical and Dental University, Tokyo, Japan.
2016 Regulation of Genome Stability, Telomeres, and the Epigenome by ZSCAN4; Genome Stability and Epigenomic Regulation in Stem Cells by ZSCAN4. Graduate Education Course in Oncology, Kyoto University, Kyoto, Japan.
2016 Toward healthy longevity through systems medicine – Perspectives from my 30-year research experience in the US and Japan. International Symposium, Promotion of Research and Development in the Medical Field in Okinawa, Okinawa, Japan.
2016 Systems analysis of transcription factor networks: Toward precise control of differentiation in human and mouse ES cells. 135th RIKEN BioResource Center Seminar, Tsukuba, Japan.
2016 The ZSCAN4 gene responsible for genome stability in stem cells: Epigenomic regulatory mechanisms and their therapeutic applications. 35th Meeting of the Japanese Society for Molecular Pathology, Hiyoshi, Japan.
2017 6th Area Meeting & JST–OIST Joint Seminar, Okinawa
2018 Next-Generation Bio and Medical Technology Exploratory Research Meeting, University of Tokyo
2018 Central Institute for Experimental Animals, Academic Colloquium: “Differentiation Technologies of Human iPS/ES Cells into Diverse Cell Types Created by Systems Approaches: Prospects for Drug Discovery and Regenerative Medicine”
2019 Tokyo Medical Association, “Meeting to Support Medical Students, Residents, and Others”
■ List of Scientific Publications
● Peer-Reviewed Publications (*corresponding author)
1. Noda M, Ko M, Ogura A, Liu D-G, Amano T, Takano T, and Ikawa Y. (1985). Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature 318: 73-78. https://pubmed.ncbi.nlm.nih.gov/4058592/
*2. Ko MSH and Takano T. (1989). A highly inducible system of gene expression by positive feedback production of glucocorticoid receptors. DNA 8: 127-133. https://pubmed.ncbi.nlm.nih.gov/2494026/
*3. Ko MSH, Takahashi N, Sugiyama N, and Takano T. (1989). An auto-inducible vector conferring high glucocorticoid-inducibility upon stable transformant cells. Gene 84: 383-389. https://pubmed.ncbi.nlm.nih.gov/2558971/
*4. Ko MSH, Ko SBH, Takahashi N, Nishiguchi K, and Abe K. (1990). Unbiased amplification of a highly complex mixture of DNA fragments by "lone linker"-tagged PCR. Nucleic Acids Research 18: 4293-4294. https://pubmed.ncbi.nlm.nih.gov/2377489/
*5. Ko MSH, Nakauchi H, and Takahashi N. (1990). The dose-dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO Journal 9: 2834-2882. https://pubmed.ncbi.nlm.nih.gov/2167833/
*6. Ko MSH. (1990). An "equalized cDNA library" by the reassociation of short double-stranded cDNAs. Nucleic Acids Research 18: 5705-5711. https://pubmed.ncbi.nlm.nih.gov/2216762/
*7. Ko MSH. (1991). A stochastic model for gene induction. J Theor Biol 153: 181-184. https://pubmed.ncbi.nlm.nih.gov/1787735/
*8. Ko MSH. (1992). Induction mechanism of a single gene molecule: Stochastic or Deterministic? BioEssays 14: 341-346. . https://pubmed.ncbi.nlm.nih.gov/1637366/
*9. Takahashi N and Ko MSH. (1993). The short 3′-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome. Genomics 16, 161-168. https://pubmed.ncbi.nlm.nih.gov/8486351/
10. Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko MSH, Thurston SJ and Birkenmeier EH. (1994). Maps from two interspecific backcross DNA panels are available as a community genetic mapping resource. Mamm. Genome 5: 253-274. https://pubmed.ncbi.nlm.nih.gov/8075499/
*11. Horton JH, Hagen MD and Ko MSH. (1994). Optimized conditions for cycle sequencing of PCR products. PCR Methods & Applications 3: 359-360. https://pubmed.ncbi.nlm.nih.gov/7920241/
*12. Wang X., Qian J. and Ko MSH. (1994). Simple and robust screening of pooled YAC libraries by the restriction enzyme digestion of PCR products. Genet. Anal. Techn. Appl. 11: 63-68. https://pubmed.ncbi.nlm.nih.gov/7803131/
13. Ko MSH*, Wang X, Horton JH, Hagen MD, Takahashi N, Maezaki Y and Nadeau JH (1994). Genetic mapping of 40 cDNA clones on the mouse genome by PCR. Mamm. Genome. 5: 349-355. https://pubmed.ncbi.nlm.nih.gov/8043949/
*14. Takahashi N and Ko MSH. (1994). Towards a whole cDNA catalog: an equalized cDNA library from mouse embryos. Genomics. 23: 202-210. https://pubmed.ncbi.nlm.nih.gov/7829072/
15. Harada H, Hashimoto K and Ko MSH. (1996). The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J. Invest. Dermatology, 107: 41-43. https://pubmed.ncbi.nlm.nih.gov/8752837/
*16. Yotsumoto S, Fujiwara H, Horton JH, Mosby TA, Wang X, Cui Y and Ko MSH. (1996). Cloning and expression analyses of mouse dystroglycan gene: Specific expression in maternal decidua at the peri-implantation stage. Hum Mol Genet, 5: 1259-1267. https://pubmed.ncbi.nlm.nih.gov/8872465/
17. Harada H, Hashimoto K, Toi Y, Yotsumoto S and Ko MSH. (1997). Basal cell carcinoma occurring in multiple familial trichoepithelioma: detection of loss of heterozygosity in chromosome 9q. Arch Dermatol, 133: 666-667. https://pubmed.ncbi.nlm.nih.gov/9158430/
18. D’Esposito M, Matarazzo MR, Ciccodicola A, Strazzullo M, Mazzarella R, Quaderi NA, Fujiwara H, Ko MSH, Rowe LB, Ricco A, Archidiacono N, Rocchi M, Schlessinger D and D’Urso M. (1997). Differential expression pattern of XqPAR-linked genes SYBL1 and IL9R correlates with the structure and evolution of the region. Hum Mol Genet, 6: 1917-1923. https://pubmed.ncbi.nlm.nih.gov/9302271/
19. Srivastava AK, Pispa J, Hartung AJ, Du Y, Ezer S, Jenks T, Shimada T, Pekkanen M, Ko MSH, Thesleff I, Kere J and Schlessinger D. (1997). The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene, which reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains. Proc. Natl. Acad. Sci. USA, 94: 13069-13074. https://pubmed.ncbi.nlm.nih.gov/9371801/
20. Jaradat SA, Ko MSH and Grossman LI. (1998). Tissue specific expression and mapping of the COX7AH gene in mouse. Genomics, 49: 363-370. https://pubmed.ncbi.nlm.nih.gov/9615220/
*21. Yotsumoto S, Shimada T, Cui CY, Nakashima H, Fujiwara H and Ko MSH. (1998). Expression of Adrenomedullin, a Hypotensive Peptide, in the Trophoblast Giant Cells at the Embryo Implantation Site in Mouse. Dev Biol, 203: 264-275. https://pubmed.ncbi.nlm.nih.gov/9808778/
*22. Ko MSH, Threat TA, Wang X, Horton JH, Cui Y, Pryor E, Paris J, Wells-Smith J, Kitchen JR, Rowe LB, Eppig J, Satoh T, Brant L, Fujiwara H, Yotsumoto S and Nakashima H (1998). Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome. Hum Mol Genet, 7: 1967-78. https://pubmed.ncbi.nlm.nih.gov/9811942/
23. Schlessinger D and Ko MSH (1998). Developmental Genomics and Its Relation to Aging. Genomics. 52, 113-118. https://pubmed.ncbi.nlm.nih.gov/10348638/
24. Abe K, Ko MSH and MacGregor G.R. (1998). A systematic molecular genetic approach to study mammalian germline development. Int. J. Dev. Biol. 42, 1051-1066. https://pubmed.ncbi.nlm.nih.gov/9853837/
*25. Nakashima H, Grahovac MJ, Mazzarella R, Kitchen JR, Threat TA and Ko MSH. (1999). Two novel mouse genes – Nubp2, mapped to the t-complex on Chromosome 17, and Nubp1, mapped to Chromosome 16 – establish a new gene family of nucleotide binding proteins in eukaryotes. Genomics, 60: 152-160. https://pubmed.ncbi.nlm.nih.gov/10486206/
26. Leach R, Ko MSH, Krawetz S. (1999). Assignment of amyloid-precursor-like protein 2 gene (APLP2) to 11q24 by fluorescent in situ hybridization. Cytogenet Cell Genet, 87: 215-216. https://pubmed.ncbi.nlm.nih.gov/10702673/
*27. Yotsumoto S, Kanzaki T, Ko MSH. (2000). Beta subunit of the high affinity immunoglobulin E receptor, a candidate for atopic dermatitis, is not imprinted. Br J Dermatol, 142:370-371. https://pubmed.ncbi.nlm.nih.gov/10730778/
*28. Ko MSH, Kitchen JR, Wang X., Threat TA, Wang X, Hasegawa A, Sun T, Grahovac MJ, Kargul GJ, Lim MK, Cui Y, Sano Y, Tanaka T, Liang Y, Mason S, Paonessa PD, Sauls AD, DePalma GE, Sharara R, Rowe LB, Eppig J, Morrell C, Doi H (2000). Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development. Development, 127: 1737-1749. https://pubmed.ncbi.nlm.nih.gov/10725249/
29. Chou SR, Brownell A, Ko MSH, Kaplan J. (2000). Interferon gamma receptor gene: key role in determining accessibility of NK-triggering antigens to recognition by Self-reactive NK cells. Cell Immunol. 2000 Mar 15;200(2):88-97. https://pubmed.ncbi.nlm.nih.gov/10753500/
*30. Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood 3 WH, Becker KG, and Ko MSH (2000). Genome-wide expression profiling of mid-gestation placenta and embryo using a 15000 mouse developmental cDNA microarray, Proc. Natl. Acad. Sci. USA, 97: 9127-9132. https://pubmed.ncbi.nlm.nih.gov/10922068/
*31. Kargul GJ, Nagaraja R, Shimada T, Grahovac M, Lim MK, Nakashima H, Waeltz P, Ma P, Chen E, Schlessinger D and Ko MSH (2000). Eleven densely clustered genes, seven of them novel, in 176 kb of mouse t-complex DNA. Genome Res, 10: 916-923. https://pubmed.ncbi.nlm.nih.gov/10899141/
*32. Nicholson RH, Pantano S, Eliason JF, Galy A, Weiler S, Kaplan J, Hughes MR, and Ko MSH (2000). Phemx, a novel mouse gene expressed during hematopoiesis, maps to the imprinted cluster on distal chromosome 7. Genomics, 68: 13-21. https://pubmed.ncbi.nlm.nih.gov/10950922/
33. Cocchia M, Huber R, Pantano S, Chen EY, Forabosco A, Ko MSH, and Schlessinger D (2000). PLAC1, an Xq26 gene with placenta-specific expression. Genomics, 68: 305-312. https://pubmed.ncbi.nlm.nih.gov/10995572/
*34. Ko MSH (2001). Embryogenomics: developmental biology meets genomics. Trends Biotechnol. 19: 511-518. https://pubmed.ncbi.nlm.nih.gov/11711195/
*35. Kargul GJ, Dudekula DB, Qian Y, Lim MK, Jaradat SA, Tanaka TS, Carter MG, and Ko MSH (2001). Verification and initial annotation of the NIA mouse 15K cDNA clone set. Nature Genetics, 28:17-18. https://pubmed.ncbi.nlm.nih.gov/11326268/
36. Cintron VJ, Ko MSH, Chi KD, Gross JP, Srinivas PR, Goustin AS, Grunberger G (2001). Genetic mapping and functional studies of a natural inhibitor of the insulin receptor tyrosine kinase: the mouse ortholog of human alpha2-HS glycoprotein. Int J Exp Diabetes Res, 1: 249-263. https://pubmed.ncbi.nlm.nih.gov/11467416/
*37. Piao Y, Ko NT, Lim MK, Ko MSH (2001). Construction of long-transcript enriched cDNA libraries from submicrogram amounts of total RNAs by a universal PCR amplification method. Genome Res. 11: 1553-1558. https://pubmed.ncbi.nlm.nih.gov/11544199/
38. Barrett T, Xie T, Piao Y, Dillon-Carter O, Kargul GJ, Lim MK, Chrest FJ, Wersto R, Rowley DL, Juhaszova M, Zhou L, Vawter MP, Becker KG, Cheadle C, Wood WH 3rd, McCann UD, Freed WJ, Ko MSH, Ricaurte GA, Donovan DM (2001). A Murine Dopamine Neuron-Specific cDNA Library and Microarray: Increased COXI Expression during Methamphetamine Neurotoxicity. Neurobiol Dis. 8: 822-833. https://pubmed.ncbi.nlm.nih.gov/11592851/
39. Hudson TJ, Church DM, Greenaway S, Nguyen H, Cook A, Steen RG, Van Etten WJ, Castle AB, Strivens MA, Trickett P, Heuston C, Davison C, Southwell A, Hardisty R, Varela-Carver A, Haynes AR, Rodriguez-Tome P, Doi H, Ko MSH, Pontius J, Schriml L, Wagner L, Maglott D, Brown SD, Lander ES, Schuler G, Denny P (2001). A radiation hybrid map of mouse genes. Nat Genet. 29: 201-205. https://pubmed.ncbi.nlm.nih.gov/11586302/
*40. Sano Y, Shimada T, Nakashima H, Nicholson RH, Eliason JF, Kocarek TA, Ko MSH (2001). Random Monoallelic Expression of Three Genes Clustered within 60 kb of Mouse t Complex Genomic DNA. Genome Res. 11: 1833-1841. https://pubmed.ncbi.nlm.nih.gov/11691847/
41. Leach R, Duniec-Dmuchowski Z, Tanaka T, Ko MSH, Krawetz SA. Assignment of OVCOV1 (alias CGI-15) to human chromosome 20 band q13.1–>q13.2 by fluorescent in situ hybridization. Cytogenet Cell Genet. 2001;94(3-4):252-3. https://pubmed.ncbi.nlm.nih.gov/11856893/
42. Cui CY, Durmowicz M, Tanaka TS, Hartung AJ, Tezuka T, Hashimoto K, Ko MSH, Srivastava AK, Schlessinger D. (2002). EDA targets revealed by skin gene expression profiles of wild-type, Tabby and Tabby EDA-A1 transgenic mice. Hum Mol Genet. 2002 Jul 15;11(15):1763-73. https://pubmed.ncbi.nlm.nih.gov/12095918/
43. Leach RE, Duniec-Dmuchowski ZM, Pesole G, Tanaka TS, Ko MSH, Armant RD, Krawetz SA. (2002). Identification, molecular characterization, and tissue expression of OVCOV1. Mamm Genome 13: 619-24. https://pubmed.ncbi.nlm.nih.gov/12461647/
*44. VanBuren V, Piao Y, Dudekula DB, Qian Y, Carter MG, Martin PR, Stagg CA, Bassey UC, Aiba K, Hamatani T, Kargul GJ, Luo AG, Kelso J, Hide W and Ko MSH. (2002). Assembly, verification, and initial annotation of the NIA mouse 7.4K cDNA clone set. Genome Res 12: 1999-2003. https://pubmed.ncbi.nlm.nih.gov/12466305/
*45. Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA, Usuda M, Yokota T, Niwa H, Rossant J, and Ko MSH. (2002). Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 12: 1921-8. https://pubmed.ncbi.nlm.nih.gov/12466296/
46. Chen G., Jaradat SA, Banerjee N, Tanaka TS, Ko MSH, and Zhang MQ (2002). Evaluation and Comparison of Clustering Algorithms in Analyzing ES Cell Gene Expression Data. Statistica Sinica 12: 241-262.
*47. Suemizu H, Aiba H, Yoshikawa T, Sharov AA, Shimozawa N, Tamaoki N, and Ko MSH. (2003). Expression profiling of placentomegaly associated with nuclear transplantation of mouse ES cells. Dev Biol 253: 36-53. https://pubmed.ncbi.nlm.nih.gov/12490196/
*48. Kimber WL, Puri N, Borgmeyer C, Ritter D, Sharov A, Seidman M, and Ko MSH. (2003). Efficacy of 2-methoxyethoxy (2’-MOE)-modified antisense oligonucleotides for the study of mouse preimplantation development. Reprod Biomed Online 6, 318-322. https://pubmed.ncbi.nlm.nih.gov/12735867/
*49. Carter MG, Hamatani T, Sharov AA, Carmack CE, Qian Y, Ko NT, Dudekula DB, Brzoska PM, Hwang SS, and Ko MSH. (2003). In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling. Genome Res. 13: 1011-21. https://pubmed.ncbi.nlm.nih.gov/12727912/
50. Galaviz-Hernandez C, Stagg C, de Ridder G, Tanaka TS, Ko MSH, Schlessinger D, Nagaraja R. (2003). Plac8 and Plac9, novel placental-enriched genes identified through microarray analysis. Gene 309: 81-9. https://pubmed.ncbi.nlm.nih.gov/12758124/
51. Buttitta L, Tanaka TS, Chen AE, Ko MSH, and Fan C.M. (2003). Microarray analysis of somitogenesis reveals novel targets of different wnt signaling pathways in the somitic mesoderm. Dev Biol. 2003 Jun 1;258(1):91-104. https://pubmed.ncbi.nlm.nih.gov/12781685/
*52. Sharov AA, Piao Y, Matoba R, Dudekula DB, Qian Y, VanBuren V, Falco G, Martin PR, Stagg CA, Bassey UC, Wang Y, Carter MG, Hamatani T, Aiba K, Akutsu H, Sharova L, Tanaka TS, Kimber WL, Yoshikawa T, Jaradat SA, Pantano S, Nagaraja R, Boheler KR, Taub D, Hodes RJ, Longo DL, Schlessinger D, Keller J, Klotz E, Kelsoe G, Umezawa A, Vescovi AL, Rossant J, Kunath T, Hogan BL, Curci A, D’Urso M, Kelso J, Hide W, Ko MSH. (2003). Transcriptome Analysis of Mouse Stem Cells and Early Embryos. PLoS Biol. 1: 410-419. https://pubmed.ncbi.nlm.nih.gov/14691545/
*53. Carter MG, Piao Y, Dudekula DB, Qian Y, VanBuren V, Sharov AA, Tanaka TS, Martin PR, Bassey UC, Stagg CA, Aiba K, Hamatani T, Matoba R, argul GJ and Ko MSH (2003). The NIA cDNA Project in mouse stem cells and early embryos. C R Biol. 2003 Oct-Nov;326(10-11):931-40. https://pubmed.ncbi.nlm.nih.gov/14744099/
*54. Hamatani T, Carter MG, Sharov AA and Ko MSH. (2004). Dynamics of global gene expression changes during mouse preimplantation development. Dev. Cell: 6, 117-131. [Published online Dec. 18, 2003] https://pubmed.ncbi.nlm.nih.gov/14723852/
55. Abe K, Yuzuriha M, Sugimoto M, Ko MSH, Brathwaite M, Waeltz P, Nagaraja R (2004). Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5. Mamm Genome 15: 265-76. https://pubmed.ncbi.nlm.nih.gov/15112104/
56. Hamatani T, Daikoku T, Wang H, Matsumoto H, Carter MG, Ko MSH, Dey SK (2004). Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10326-31. Epub 2004 Jul 01. https://pubmed.ncbi.nlm.nih.gov/15232000/
*57. Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MSH (2004). Age-associated alteration of gene expression patterns in mouse oocytes. Human Molecular Genetics; 13(19):2263-78. Epub 2004 Aug 18. https://pubmed.ncbi.nlm.nih.gov/15317747/
58. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J; MGC Project Team. (2004). The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. https://pubmed.ncbi.nlm.nih.gov/15489334/
*59. Ko MSH (2004). Embryogenomics of preimplantation mammalian development: Current Status. Reproduction, Fertility and Development 16: 79-85. https://pubmed.ncbi.nlm.nih.gov/14972105/
*60. Tanaka TS, Ko MSH. A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst. Eur J Obstet Gynecol Reprod Biol. 2004 Jul 1;115 Suppl 1:S85-91. https://pubmed.ncbi.nlm.nih.gov/15196723/
61. Ottolenghi, C., Uda, M., Hamatani, T., Crisponi, L., Garcia, Jose-Elias., Ko, M.S.H., Pilia, G., Sforza, C., Schlessinger, D., and Forabosco, A (2004). Aging of Oocyte, Ovary and Human Reproduction. Ann. New York Acad. Sci. 1034: 117-131. https://pubmed.ncbi.nlm.nih.gov/15731305/
62. Herrera L, Ottolenghi C, Garcia-Ortiz JE, Pellegrini M, Manini F, Ko MS, Nagaraja R, Forabosco A, Schlessinger D. (2005). Mouse ovary developmental RNA and protein markers from gene expression profiling. Dev Biol. 2005 Mar 15;279(2):271-90. https://pubmed.ncbi.nlm.nih.gov/15733658/
63. Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG, Witzel SD, Okano H, Ko MS, Ohlsson R, Longo DL, Feinberg AP. (2005). Loss of Imprinting of Igf2 Alters Intestinal Maturation and Tumorigenesis in Mice. Science. 2005 Feb 24. https://pubmed.ncbi.nlm.nih.gov/15731405/
*64. Sharov AA, Dudekula DB, Ko MSH (2005). A web-based tool for principal component and significance analysis of microarray data. Bioinformatics. 2005 May 15;21(10):2548-9. Epub 2005 Feb 25. https://pubmed.ncbi.nlm.nih.gov/15734774/
*65. Sharov AA, Dudekula DB, and Ko MSH (2005). Genome-wide assembly and analysis of alternative transcripts in mouse. Genome Res. 2005 May;15(5):748-54. https://pubmed.ncbi.nlm.nih.gov/15867436/
66. Akagi T, Usuda M, Matsuda T, Ko MSH, Niwa H, Asano M, Koide H, and Yokota T. (2005). Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells. Biochem Biophys Res Commun. 2005 May 27; 331(1): 23-30. https://pubmed.ncbi.nlm.nih.gov/15845352/
67. Tamura T, Thotakura P, Tanaka TS, Ko MSH, Ozato K (2005). Identification of target genes and a unique cis-element regulated by IRF-8 in developing macrophages. Blood. 2005 Jun 9; [Epub ahead of print] https://pubmed.ncbi.nlm.nih.gov/15947094/
*68. Carter MG, Sharov AA, VanBuren V, Dudekula DB, Carmack CE, Nelson C, Ko MSH (2005). Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray. Genome Biol. 2005;6(7):R61. Epub 2005 Jun 30. https://pubmed.ncbi.nlm.nih.gov/15998450/
69. Ko MSH (2005). Molecular biology of preimplantation embryos: primer for philosophical discussions. Reprod. Biomed. Online 10 Suppl 1: 80-87. https://pubmed.ncbi.nlm.nih.gov/15820015/
70. McMahan J, Cohen J, Ko MSH, Johnson M, Robertson J, Murphy T, Brinsden P, Hussein F, Savulescu J, McLaren A, McLean S, Harris J, Schulman J, Edwards R, Pedersen R, Stock G, Grudzinskas G, and Boivin J (2005). Discussion (day 2 session 2): Modern genetics and the human embryo in vitro. Reprod. Biomed. Online 10 Suppl 1: 107-110. https://pubmed.ncbi.nlm.nih.gov/15820019/
*71. Yoshikawa T, Piao Y, Zhong J, Matoba R, Carter MG, Wang Y, Goldberg I, Ko MSH (2006). High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization. Gene Expr Patterns. 2006 Jan;6(2):213-24. Epub 2005 Dec 1. https://pubmed.ncbi.nlm.nih.gov/16325481/
*72. Aiba K, Sharov AA, Carter MG, Foroni C, Vescovi AL, Ko MSH (2005). Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells. Stem Cells. 2005 Dec 15; [Epub ahead of print] https://pubmed.ncbi.nlm.nih.gov/16357342/
73. Park JM, Kohn MJ, Bruinsma MW, Vech C, Intine RV, Fuhrmann S, Grinberg A, Mukherjee I, Love PE, Ko MSH, Depamphilis ML, Maraia RJ (2006). The Multifunctional RNA-Binding Protein La Is Required for Mouse Development and for the Establishment of Embryonic Stem Cells. Mol Cell Biol. 2006 Feb;26(4):1445-51. https://pubmed.ncbi.nlm.nih.gov/16449655/
74. Das B, Cai L, Carter MG, Piao YL, Sharov AA, Ko MSH, Brown DD (2006). Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles. Dev Biol. 2006 Feb 1; [Epub ahead of print] https://pubmed.ncbi.nlm.nih.gov/16458881/
*75. Ko MSH (2006). Expression profiling of the mouse early embryo: Reflections and perspectives. Dev Dyn. 2006 May 31; [PMID: 16739220] https://pubmed.ncbi.nlm.nih.gov/16739220/
76. Rogers NT, Halet G, Piao Y, Carroll J, Ko MSH and Swann K (2006). A Ca2+ signal during mouse egg activation affects preimplantation development, gene expression patterns, and blastocyst quality. Reproduction. 2006 Jul;132(1):45-57. [PMID: 16816332] https://pubmed.ncbi.nlm.nih.gov/16816332/
*77. Tanaka TS, Lopez de Silanes I, Sharova LV, Akutsu H, Yoshikawa T, Amano H, Yamanaka S, Gorospe M, Ko MSH (2006). Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative RNA-binding protein with broad RNA targets. Dev Growth Differ. 2006 Aug;48(6):381-90. [PMID: 16872451] https://pubmed.ncbi.nlm.nih.gov/16872451/
*78. Falco G, Stanghellini I, Ko MS (2006). Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos. Reprod Biomed Online. 2006 Sep;13(3):394-403. PMID: 16984773 [PubMed – indexed for MEDLINE] https://pubmed.ncbi.nlm.nih.gov/16984773/
*79. Aiba K, Carter MG, Matoba R, Ko MSH (2006). Genomic approaches to early embryogenesis and stem cell biology. Semin Reprod Med. 2006 Nov;24(5):330-9. PMID: 17123228 https://pubmed.ncbi.nlm.nih.gov/17123228/
*80. Sharov AA, Dudekula DB, Ko MSH (2006). CisView: a browser and database of cis-regulatory modules predicted in the mouse genome. DNA Res. 2006 Jun 30;13(3):123-34. Epub 2006 Sep 15. PMID: 16980320. https://pubmed.ncbi.nlm.nih.gov/16980320/
81. Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H (2006). Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 2006 Oct;26(20):7772-82. Epub 2006 Sep 5. PMID: 16954384 [PubMed – indexed for MEDLINE] https://pubmed.ncbi.nlm.nih.gov/16954384/
82. Hamatani T, Ko MSH, Yamada M, Kuji N, Mizusawa Y, Shoji M, Hada T, Asada H, Maruyama T, Yoshimura Y (2006). Global gene expression profiling of preimplantation embryos. Hum Cell. 2006 Aug;19(3):98-117. https://pubmed.ncbi.nlm.nih.gov/17204093/
*83. Matoba R, Niwa H, Masui S, Ohtsuka S, Carter MG, Sharov AA, Ko MS (2006). Dissecting oct3/4-regulated gene networks in embryonic stem cells by expression profiling. PLoS ONE. 2006 Dec 20;1:e26. PMID: 17183653 [PubMed – as supplied by publisher] https://pubmed.ncbi.nlm.nih.gov/17183653/
84. Ko MSH and McLaren A (2006). Epigenetics of germ cells, stem cells, and early embryos. Meeting Report. Dev. Cell 10, 161-166. https://pubmed.ncbi.nlm.nih.gov/16506346/
85. Ko, MSH (2006). Meet our Editor. Reprod. Biomed. Online. 12: 143.
86. Sharov AA and Ko MSH (2007). Previews: Human ES cell profiling broadens the reach of bivalent domains. Cell Stem Cell 1, 237-238. [PMID: 18371354] https://pubmed.ncbi.nlm.nih.gov/18371354/
87. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 2007 Jun;9(6):625-35. Epub 2007 May 21. PMID: 17515932 [PubMed – indexed for MEDLINE] https://pubmed.ncbi.nlm.nih.gov/17515932/
*88. Falco G, Lee SL, Stanghellini I, Bassey UC, Hamatani T, Ko MS (2007). Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells. Dev Biol. 2007 Jul 15;307(2):539-50. Epub 2007 May 8. PMID: 17553482 [PubMed – indexed for MEDLINE] https://pubmed.ncbi.nlm.nih.gov/17553482/
*89. Sharova LV, Sharov AA, Piao Y, Shaik N, Sullivan T, Stewart CL, Hogan BL, Ko MS (2007). Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains. Dev Biol. 2007 Jul 15;307(2):446-59. Epub 2007 May 10. PMID: 17560561 [PubMed – indexed for MEDLINE] https://pubmed.ncbi.nlm.nih.gov/17560561/
90. Ulloa-Montoya F, Kidder BL, Pauwelyn KA, Chase LG, Luttun A, Crabbe A, Geraerts M, Sharov AA, Piao Y, Ko MS, Hu WS, Verfaillie CM (2007). Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity. Genome Biol. 2007 Aug 6;8(8):R163 [Epub ahead of print] PMID: 17683608 [PubMed – as supplied by publisher] https://pubmed.ncbi.nlm.nih.gov/17683608/
91. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta EG, Boheler KR, Xu X, Mattson MP, Falco G, Ko MS, Schlessinger D, Firman J, Kummerfeld SK, Wood WH 3rd, Zonderman AB, Kim SK, Becker KG. (2007). AGEMAP: a gene expression database for aging in mice. PLoS Genet. 2007 Nov 30;3(11):e201. Epub 2007 Oct 2. PMID: 18081424 [PubMed – in process] https://pubmed.ncbi.nlm.nih.gov/18081424/
92. Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP (2007). Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20926-31. Epub 2007 Dec 17. PMID: 18087038 [PubMed – in process] https://pubmed.ncbi.nlm.nih.gov/18087038/
*93. Carter MG, Stagg CA, Falco G, Yoshikawa T, Bassey UC, Aiba K, Sharova LV, Shaik N, Ko MS (2007). An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells. Gene Expr Patterns. 2007 Nov 4; [Epub ahead of print] PMID: 18178135 [PubMed – as supplied by publisher] https://pubmed.ncbi.nlm.nih.gov/18178135/
*94. Yan Z, Wang Z, Sharova L, Sharov AA, Ling C, Piao Y, Aiba K, Matoba R, Wang W, and Ko MS (2008). BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells. 2008 May;26(5):1155-65. Epub 2008 Mar 6. [PMID: 18323406] https://pubmed.ncbi.nlm.nih.gov/18323406/
95. Vallée M, Aiba K, Piao Y, Palin MF, Ko MS, and Sirard MA (2008). Comparative analysis of oocyte transcript profiles reveals a high degree of conservation among species. Reproduction. 2008 Apr;135(4):439-48. [PMID: 18367505] https://pubmed.ncbi.nlm.nih.gov/18367505/
96. Masui S, Ohtsuka S, Yagi R, Takahashi K, Ko MS, and Niwa H (2008). Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells. BMC Dev Biol. 2008 Apr 24;8:45. [PMID: 18433507] https://pubmed.ncbi.nlm.nih.gov/18433507/
*97. Sharov AA, Falco G, Piao Y, Poosala S, Becker KG, Zonderman AB, Longo DL, Schlessinger D, and Ko MSH (2008). Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary. BMC Biol. 2008 Jun 3;6:24. [PMID: 18522719] . https://pubmed.ncbi.nlm.nih.gov/18522719/
*98. Sharov AA, Masui S, Sharova LV, Piao Y, Aiba K, Matoba R, Xin L, Niwa H, and Ko MS (2008). Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data. BMC Genomics. 2008 Jun 3;9:269. [PMID: 18522731] https://pubmed.ncbi.nlm.nih.gov/18522731/
99. Tsuji Y, Yoshimura N, Aoki H, Sharov AA, Ko MS, Motohashi T, and Kunisada T (2008). Maintenance of undifferentiated mouse embryonic stem cells in suspension by the serum- and feeder-free defined culture condition. Dev Dyn. 2008 Aug;237(8):2129-38. [PMID: 18624284] https://pubmed.ncbi.nlm.nih.gov/18624284/
*100. Yellaboina S, Dudekula DB, and Ko MSH (2008). Prediction of evolutionarily conserved interologs in Mus musculus. BMC Genomics. 2008 Oct 8;9:465. [PMID: 18842131] https://pubmed.ncbi.nlm.nih.gov/18842131/
101. Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, and Wu C (2008). Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet. 2008 Oct;4(10):e1000241. [PMID: 18974875] https://pubmed.ncbi.nlm.nih.gov/18974875/
*102. Aiba K, Nedorezov T, Piao Y, Nishiyama A, Matoba R, Sharova LV, Sharov AA, Yamanaka S, Niwa H, Ko MS (2009). Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells. DNA Res. 2009 Feb;16(1):73-80. Epub 2008 Dec 26. PMID: 19112179 [PMCID: PMC2644347] https://pubmed.ncbi.nlm.nih.gov/19112179/
103. Kunisada M, Cui CY, Piao Y, Ko MS, Schlessinger D (2009). Requirement for Shh and Fox family genes at different stages in sweat gland development. Hum Mol Genet. 2009 May 15;18(10):1769-78. Epub 2009 Mar 6. PMID: 19270025 [PMCID: PMC2671986] https://pubmed.ncbi.nlm.nih.gov/19270025/
104. Sun C, Nakatake Y, Akagi T, Ura H, Matsuda T, Nishiyama A, Koide H, Ko MS, Niwa H, Yokota T (2009). Dax1 Binds to Oct3/4 and Inhibits Its Transcriptional Activity in Embryonic Stem Cells. Mol Cell Biol. 2009 Jun 15. [PMID: 19528230] https://pubmed.ncbi.nlm.nih.gov/19528230/
*105. Stanghellini I, Falco G, Lee SL, Monti M, Ko MS (2009). Trim43a, Trim43b, and Trim43c: Novel mouse genes expressed specifically in mouse preimplantation embryos. Gene Expr Patterns. 2009 Dec;9(8):595-602. Epub 2009 Aug 22. PMID: 19703589. https://pubmed.ncbi.nlm.nih.gov/19703589/
*106. Sharov AA, Ko MS (2009). Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res. 2009 Oct;16(5):261-73. Epub 2009 Sep 9. PMID: 19740934. https://pubmed.ncbi.nlm.nih.gov/19740934/
107. Vallejo G, Maschi D, Mestre-Citrinovitz AC, Aiba K, Maronna R, Yohai V, Ko MS, Beato M, Saragüeta P (2010). Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells. J Cell Physiol. 2010 Jan;222(1):127-37. PMID: 19780023. https://pubmed.ncbi.nlm.nih.gov/19780023/
*108. Nishiyama A, Xin L, Sharov AA, Thomas M, Mowrer G, Meyers E, Piao Y, Mehta S, Yee S, Nakatake Y, Stagg C, Sharova L, Correa-Cerro LS, Bassey U, Hoang H, Kim E, Tapnio R, Qian Y, Dudekula D, Zalzman M, Li M, Falco G, Yang HT, Lee SL, Monti M, Stanghellini I, Islam MN, Nagaraja R, Goldberg I, Wang W, Longo DL, Schlessinger D, Ko MS (2009). Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009 Oct 2;5(4):420-33. PMID: 19796622. [PMC2770715] https://pubmed.ncbi.nlm.nih.gov/19796622/
*109. Sharova LV, Sharov AA, Nedorezov T, Piao Y, Shaik N, Ko MS (2009). Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res 2009; 16(1): 45-58. [PMC2644350] https://pubmed.ncbi.nlm.nih.gov/19001483/
110. Canham MA, Sharov AA, Ko MS, Brickman JM (2010). Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript. PLoS Biol 2010; 8(5): e1000379. [PMC2876051] https://pubmed.ncbi.nlm.nih.gov/20520791/
111. Cui CY, Kunisada M, Piao Y, Childress V, Ko MS, Schlessinger D (2010). Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair. PLoS One 2010; 5(4): e10009. [PMC2850388] https://pubmed.ncbi.nlm.nih.gov/20386733/
*112. Sharov AA, Piao Y, Ko MS (2010). Gene expression profiling of mouse embryos with microarrays. Methods Enzymol 2010; 477: 511-41. [PMC3166619] https://pubmed.ncbi.nlm.nih.gov/20699157/
113. Vong QP, Liu Z, Yoo JG, Chen R, Xie W, Sharov AA, Fan CM, Liu C, Ko MS, Zheng Y (2010). A role for borg5 during trophectoderm differentiation. Stem Cells 2010; 28(6): 1030-8. [PMC2957878] https://pubmed.ncbi.nlm.nih.gov/20506138/
*114. Zalzman M, Falco G, Sharova LV, Nishiyama A, Thomas M, Lee SL, Stagg CA, Hoang HG, Yang HT, Indig FE, Wersto RP, Ko MS (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 2010; 464(7290): 858-63. [PMC2851843] https://pubmed.ncbi.nlm.nih.gov/20336070/
*115. Correa-Cerro LS, Piao Y, Sharov AA, Nishiyama A, Cadet JS, Yu H, Sharova LV, Xin L, Hoang HG, Thomas M, Qian Y, Dudekula DB, Meyers E, Binder BY, Mowrer G, Bassey U, Longo DL, Schlessinger D, Ko MS (2011). Generation of mouse ES cell lines engineered for the forced induction of transcription factors. Sci Rep 2011; 1: 167. [PMC3240988] https://pubmed.ncbi.nlm.nih.gov/22355682/
*116. Kim Y, Sharov AA, McDole K, Cheng M, Hao H, Fan CM, Gaiano N, Ko MS, Zheng Y (2011). Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. Science 2011; 334(6063): 1706-10. [PMC3306219] https://pubmed.ncbi.nlm.nih.gov/22116031/
*117. Sharov AA, Nishiyama A, Piao Y, Correa-Cerro LS, Amano T, Thomas M, Mehta S, Ko MS (2011). Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity. BMC Genomics 2011; 12: 102. [PMC3044670] https://pubmed.ncbi.nlm.nih.gov/21306619/
118. Cui CY, Childress V, Piao Y, Michel M, Johnson AA, Kunisada M, Ko MS, Kaestner KH, Marmorstein AD, Schlessinger D (2012). Forkhead transcription factor FoxA1 regulates sweat secretion through Bestrophin 2 anion channel and Na-K-Cl cotransporter 1. Proc Natl Acad Sci U S A 2012; 109(4): 1199-203. [PMC3268268] https://pubmed.ncbi.nlm.nih.gov/22223659/
119. Hammachi F, Morrison GM, Sharov AA, Livigni A, Narayan S, Papapetrou EP, O’Malley J, Kaji K, Ko MS, Ptashne M, Brickman JM (2012). Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency. Cell Rep 2012; 1(2): 99-109. https://pubmed.ncbi.nlm.nih.gov/22832160/
*120. Hirata T, Amano T, Nakatake Y, Amano M, Piao Y, Hoang HG, Ko MS (2012). Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells. Sci Rep 2012; 2: 208. [PMC3250575] https://pubmed.ncbi.nlm.nih.gov/22355722/
121. Ko SB, Azuma S, Yoshikawa T, Yamamoto A, Kyokane K, Ko MS, Ishiguro H (2012). Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. Front Physiol 2012; 3: 415. [PMC3488765] https://pubmed.ncbi.nlm.nih.gov/23133422/
122. States JC, Singh AV, Knudsen TB, Rouchka EC, Ngalame NO, Arteel GE, Piao Y, Ko MS (2012). Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis. PLoS One 2012; 7(6): e38713. [PMC3376138] https://pubmed.ncbi.nlm.nih.gov/22719926/
123. Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK (2012). Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem 2012; 287(38): 32288-97. [PMC3442559] https://pubmed.ncbi.nlm.nih.gov/22833670/
*124. Yang HT, Ko MS (2012). Stochastic modeling for the expression of a gene regulated by competing transcription factors. PLoS One 2012; 7(3): e32376. [PMC3303788] https://pubmed.ncbi.nlm.nih.gov/22431973/
*125. Hung SS, Wong RC, Sharov AA, Nakatake Y, Yu H, Ko MS (2013). Repression of global protein synthesis by eif1a-like genes that are expressed specifically in the two-cell embryos and the transient zscan4-positive state of embryonic stem cells. DNA Res 2013; 20(4): 391-402. [PMC3738165] https://pubmed.ncbi.nlm.nih.gov/23649898/
126. Ko SB, Azuma S, Yokoyama Y, Yamamoto A, Kyokane K, Niida S, Ishiguro H, Ko MS (2013). Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas. Am J Physiol Gastrointest Liver Physiol 2013; 304(12): G1103-16. [PMC3680719] https://pubmed.ncbi.nlm.nih.gov/23599043/
127. Monti M, Zanoni M, Calligaro A, Ko MS, Mauri P, Redi CA (2013). Developmental arrest and mouse antral not-surrounded nucleolus oocytes. Biol Reprod 2013; 88(1): 2. https://pubmed.ncbi.nlm.nih.gov/23136301/
128. Morgani SM, Canham MA, Nichols J, Sharov AA, Migueles RP, Ko MS, Brickman JM (2013). Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep 2013; 3(6): 1945-57. [PMC3701323] https://pubmed.ncbi.nlm.nih.gov/23746443/
*129. Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T, Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS (2013). Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep 2013; 3: 1390. [PMC3589720] https://pubmed.ncbi.nlm.nih.gov/23462645/
*130. Amano T, Hirata T, Falco G, Monti M, Sharova LV, Amano M, Sheer S, Hoang HG, Piao Y, Stagg CA, Yamamizu K, Akiyama T, Ko MS (2013). Zscan4 restores the developmental potency of embryonic stem cells. Nat Commun 2013; 4: 1966. [PMC3682791] https://pubmed.ncbi.nlm.nih.gov/23739662/
131. Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, Yang J, Sharov A, Srikantan S, Yang J, Fox D, 3rd, Qian Y, Martindale JL, Piao Y, Machamer J, Joshi SR, Mohanty S, Shaw AC, Lloyd TE, Brown GW, Ko MS, Gorospe M, Zou S, Wang W (2013). Top3beta is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci 2013. https://pubmed.ncbi.nlm.nih.gov/23912945/
132. Livigni A, Peradziryi H, Sharov AA, Chia G, Hammachi F, Migueles RP, Sukparangsi W, Pernagallo S, Bradley M, Nichols J, Ko MS, Brickman JM (2013). A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. Curr Biol. 2013 Nov 18;23(22):2233-44. doi:10.1016/j.cub.2013.09.048. PMID:24210613 https://pubmed.ncbi.nlm.nih.gov/24210613/
*133. Yamamizu K, Piao Y, Sharov AA, Zsiros V, Yu H, Nakazawa K, Schlessinger D, Ko MS (2013). Identification of transcription factors for lineage-specific ESC differentiation. Stem Cell Reports. 2013 Nov 27;1(6):545-59. doi: 10.1016/j.stemcr.2013.10.006. PMID:24371809 https://pubmed.ncbi.nlm.nih.gov/24371809/
134. Sherman-Baust CA, Kuhn E, Valle BL, Shih IeM, Kurman RJ, Wang TL, Amano T, Ko MS, Miyoshi I, Araki Y, Lehrmann E, Zhang Y, Becker KG, Morin PJ (2014). A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 2014 Jul;233(3):228-37. doi: 10.1002/path.4353. PMID:24652535 https://pubmed.ncbi.nlm.nih.gov/24652535/
*135. Piao Y, Hung SS, Lim SY, Wong RC, Ko MS (2014). Efficient generation of integration-free human induced pluripotent stem cells from keratinocytes by simple transfection of episomal vectors. Stem Cells Transl Med. 2014 Jul;3(7):787-91. doi: 10.5966/sctm.2013-0036. PMID:24904173 https://pubmed.ncbi.nlm.nih.gov/24904173/
*136. Sharov AA, Nishiyama A, Qian Y, Dudekula DB, Longo DL, Schlessinger D, Ko MS (2014). Chromatin properties of regulatory DNA probed by manipulation of transcription factors. J Comput Biol. 2014 Aug;21(8):569-77. doi: 10.1089/cmb.2013.0126. PMID:24918633 https://pubmed.ncbi.nlm.nih.gov/24918633/
*137. Yamamizu K, Schlessinger D, Ko MS (2014). SOX9 accelerates ESC differentiation to three germ layer lineages by repressing SOX2 expression through P21 (WAF1/CIP1). Development. 2014 Nov;141(22):4254-66. doi: 10.1242/dev.115436. PMID:25371362 https://pubmed.ncbi.nlm.nih.gov/25371362/
*138. Sharov AA, Schlessinger D, Ko MS (2015). ExAtlas: An interactive online tool for meta-analysis of gene expression data. J Bioinform Comput Biol. 2015 Dec;13(6):1550019. doi: 10.1142/S0219720015500195. PMID:26223199 https://pubmed.ncbi.nlm.nih.gov/26223199/
*139. Amano T, Jeffries E, Amano M, Ko AC, Yu H, Ko MS (2015). Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. DNA Res. 2015 Oct;22(5):331-42. doi: 10.1093/dnares/dsv016. PMID:26324424 https://pubmed.ncbi.nlm.nih.gov/26324424/
*140. Akiyama T, Xin L, Oda M, Sharov AA, Amano M, Piao Y, Cadet JS, Dudekula DB, Qian Y, Wang W, Ko SB, Ko MS (2015). Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells. DNA Res. 2015 Oct;22(5):307-18. doi: 10.1093/dnares/dsv013. PMID:26324425 https://pubmed.ncbi.nlm.nih.gov/26324425/
141. Motohashi T, Watanabe N, Nishioka M, Nakatake Y, Yulan P, Mochizuki H, Kawamura Y, Ko MS, Goshima N, Kunisada T (2016). Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells. Biol Open. 2016 Feb 12;5(3):311-22. doi: 10.1242/bio.015735. PMID:26873953 https://pubmed.ncbi.nlm.nih.gov/26873953/
*142. Sharova LV, Sharov AA, Piao Y, Stagg CA, Amano T, Qian Y, Dudekula D, Schlessinger D, Ko MS (2016). Emergence of undifferentiated colonies from mouse embryonic stem cells undergoing differentiation by retinoic acid treatment. In Vitro Cell Dev Biol Anim. 2016 May;52(5):616-24. doi: 10.1007/s11626-016-0013-5. PMID:27130680 https://pubmed.ncbi.nlm.nih.gov/27130680/
*143. Yamamizu K, Sharov AA, Piao Y, Amano M, Yu H, Nishiyama A, Dudekula DB, Schlessinger D, Ko MS (2016). Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines. Sci Rep. 2016 May 6;6:25667. doi: 10.1038/srep25667. PMID:27150017 https://pubmed.ncbi.nlm.nih.gov/27150017/
*144. Ko MS (2016). Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4. Curr Top Dev Biol. 2016;120:103-24. doi: 10.1016/bs.ctdb.2016.04.004. PMID:27475850 https://pubmed.ncbi.nlm.nih.gov/27475850/
*145. Ishiguro KI, Nakatake Y, Chikazawa-Nohtomi N, Kimura H, Akiyama T, Oda M, Ko SB, Ko MS (2016). Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos. In Vitro Cell Dev Biol Anim. 2016 Oct 3. PMID:27699651 https://pubmed.ncbi.nlm.nih.gov/27699651/
*146. Ishiguro KI, Monti M, Akiyama T, Kimura H, Chikazawa-Nohtomi N, Sakota M, Sato S, Redi CA, Ko SB, Ko MS (2016). Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis. In Vitro Cell Dev Biol Anim. 2016 Oct 3. PMID:27699653 https://pubmed.ncbi.nlm.nih.gov/27699653/
147. Teratani-Ota Y, Yamamizu K, Piao Y, Sharova L, Amano M, Yu H, Schlessinger D, Ko MS, Sharov AA (2016). Induction of specific neuron types by overexpression of single transcription factors. In Vitro Cell Dev Biol Anim. 2016 Oct;52(9):961-973. PMID:27251161 https://pubmed.ncbi.nlm.nih.gov/27251161/
*148. Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SB, Ko MS (2016). Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells. Development. 2016 Oct 15;143(20):3674-3685. PMID:27802135 https://pubmed.ncbi.nlm.nih.gov/27802135/
*149. Hirayama M, Ko SB, Kawakita T, Akiyama T, Goparaju SK, Soma A, Nakatake Y, Sakota M, Chikazawa-Nohtomi N, Shimmura S, Tsubota K, Ko MS (2017). Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells. npj Aging and Mechanisms of Disease 2017; 3: 1. doi:10.1038/s41514-016-0001-8 https://pubmed.ncbi.nlm.nih.gov/28649419/
*150. Goparaju SK, Kohda K, Ibata K, Soma A, Nakatake Y, Akiyama T, Wakabayashi S, Matsushita M, Sakota M, Kimura H, Yuzaki M, Ko SB, Ko MS (2017). Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci Rep. 2017 Feb 13;7:42367. doi: 10.1038/srep42367. PMID: 28205555 https://pubmed.ncbi.nlm.nih.gov/28205555/
151. Matsumoto H, Kiryu H, Furusawa C, Ko MS, Ko SB, Gouda N, Hayashi T, Nikaido I (2017). SCODE: An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation. Bioinformatics. 2017 Apr 4. doi: 10.1093/bioinformatics/btx194. PMID:28379368 https://pubmed.ncbi.nlm.nih.gov/28379368/
152. Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E (2017). Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. Sci Rep. 2017 Apr 20;7:46580. doi: 10.1038/srep46580. PMID:28425456 https://pubmed.ncbi.nlm.nih.gov/28425456/
*153. Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Ko MSH (2017). Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells. Stem Cells Int. 2017; 2017:7215010. doi: 10.1155/2017/7215010. Epub 2017 Apr 9. Review. PMID:28491098 https://pubmed.ncbi.nlm.nih.gov/28491098/
*154. Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH (2017). Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun. 2017 Aug 19;490(2):296-301. Doi 10.1016/j.bbrc.2017.06.039. Epub 2017 Jun 10. PMID: 28610919 https://pubmed.ncbi.nlm.nih.gov/28610919/
*155. Akiyama T, Sato S, Chikazawa-Nohtomi N, Soma A, Kimura H, Wakabayashi S, Ko SBH, Ko MSH (2018). Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing. Sci Rep. 2018 Jan 19;8(1):1189. doi: 10.1038/s41598-017-19114-y. PMID: 29352121 https://pubmed.ncbi.nlm.nih.gov/29352121/
156. Ida H, Akiyama T, Ishiguro K, Goparaju SK, Nakatake Y, Chikazawa-Nohtomi N, Sato S, Kimura H, Yokoyama Y, Nagino M, Ko MSH, Ko SBH (2018). Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors. Stem Cell Res Ther. 2018 Oct 25;9(1):277. doi: 10.1186/s13287-018-1038-3. https://pubmed.ncbi.nlm.nih.gov/30359326/
*157. Hiratsuka K, Monkawa T, Akiyama T, Nakatake Y, Oda M, Goparaju SK, Kimura H, Chikazawa-Nohtomi N, Sato S, Ishiguro K, Yamaguchi S, Suzuki S, Morizane R, Ko SBH, Itoh H, Ko MSH (2019). Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. Sci Rep. 2019 Jan 29;9(1):913. doi: 10.1038/s41598-018-37485-8. PMID: 30696889 Free PMC Article https://pubmed.ncbi.nlm.nih.gov/30696889/
158. Nishihara K, Shiga T, Nakamura E, Akiyama T, Sasaki T, Suzuki S, Ko MSH, Tada N, Okano H, Akamatsu W (2019). Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression. Stem Cell Reports. 2019 Feb 12;12(2):305-318. doi: 10.1016/j.stemcr.2018.12.018. Epub 2019 Jan 31. PMID: 30713040 Free PMC Article https://pubmed.ncbi.nlm.nih.gov/30713040/
159. Ishiguro KI, Matsuura K, Tani N, Takeda N, Usuki S, Yamane M, Sugimoto M, Fujimura S, Hosokawa M, Chuma S, Ko MSH, Araki K, Niwa H (2020). MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. Dev Cell. 2020 Feb 24;52(4):429-445.e10. doi: 10.1016/j.devcel.2020.01.010. Epub 2020 Feb 6. PMID: 32032549 https://pubmed.ncbi.nlm.nih.gov/32032549/
*160. Nakatake Y, Ko SBH, Sharov AA, Wakabayashi S, Murakami M, Sakota M, Chikazawa N, Ookura C, Sato S, Ito N, Ishikawa-Hirayama M, Mak SS, Jakt LM, Ueno T, Hiratsuka K, Matsushita M, Goparaju SK, Akiyama T, Ishiguro KI, Oda M, Gouda N, Umezawa A, Akutsu H, Nishimura K, Matoba R, Ohara O, Ko MSH (2020). Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors. Cell Rep. 2020 May 19;31(7):107655. doi: 10.1016/j.celrep.2020.107655. PMID: 32433964 https://pubmed.ncbi.nlm.nih.gov/32433964/
161. Tanosaki S, Tohyama S, Fujita J, Someya S, Hishiki T, Matsuura T, Nakanishi H, Ohto-Nakanishi T, Akiyama T, Morita Y, Kishino Y, Okada M, Tani H, Soma Y, Nakajima K, Kanazawa H, Sugimoto M, Ko MSH, Suematsu M, Fukuda K (2020). Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells. iScience. 2020 Sep 6;23(9):101535. doi: 10.1016/j.isci.2020.101535. https://pubmed.ncbi.nlm.nih.gov/33083764/
162. Akiyama T, Sato S, Ko SBH, Sano O, Sato S, Saito M, Nagai H, Ko MSH, Iwata H (2020). Synthetic mRNA-based differentiation method enables early detection of Parkinson’s phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells. Stem Cells Transl Med. 2021 Apr;10(4):572-581. doi: 10.1002/sctm.20-0302. Epub 2020 Dec 20. PMID: 33342090 https://pubmed.ncbi.nlm.nih.gov/33342090/
163. Makino K, Shimizu-Hirota R, Goda N, Hashimoto M, Kawada I, Kashiwagi K, Hirota Y, Itoh H, Jinzaki M, Iwao Y, Ko M, Ko S, Takaishi H (2021). Unbiased, comprehensive analysis of Japanese health checkup data reveals a protective effect of light to moderate alcohol consumption on lung function. Sci Rep. 2021 Aug 5;11(1):15954. doi: 10.1038/s41598-021-95515-4. PMID: 34354190 https://pubmed.ncbi.nlm.nih.gov/34354190/
164. Tanosaki S, Akiyama T, Kanaami S, Fujita J, Ko MSH, Fukuda K, Tohyama S (2022). Purification of cardiomyocytes and neurons derived from human pluripotent stem cells by inhibition of de novo fatty acid synthesis. STAR Protoc. 2022 Apr 28;3(2):101360. doi: 10.1016/j.xpro.2022.101360. eCollection 2022 Jun 17. PMID: 35516845 https://pubmed.ncbi.nlm.nih.gov/35516845/
*165. Amano T, Yu H, Amano M, Leyder E, Badiola M, Ray P, Kim J, Ko AC, Achour A, Weng NP, Kochba E, Levin Y, Ko MSH (2023). Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity. iScience. 2023 Mar 5;26(4):106335. doi10.1016/j.isci.2023.106335. eCollection 2023 Apr 21. PMID: 36968065 https://pubmed.ncbi.nlm.nih.gov/36968065/
166. Kobori C, Takagi R, Yokomizo R, Yoshihara S, Mori M, Takahashi H, Javaregowda PK, Akiyama T, Ko MSH, Kishi K, Umezawa A (2023). Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3. Stem Cell Res Ther. 2023 Sep 8;14(1):242. doi: 10.1186/s13287-023-03479-1. PMID: 37679843. https://pubmed.ncbi.nlm.nih.gov/37679843/
167. Choy C, Chen J, Li J, Gallagher DT, Lu J, Wu D, Zou A, Hemani H, Baptiste BA, Wichmann E, Yang Q, Ciffelo J, Yin R, McKelvy J, Melvin D, Wallace T, Dunn C, Nguyen C, Chia CW, Fan J, Ruffolo J, Zukley L, Shi G, Amano T, An Y, Meirelles O, Wu WW, Chou CK, Shen RF, Willis RA, Ko MSH, Liu YT, De S, Pierce BG, Ferrucci L, Egan J, Mariuzza R, Weng NP (2023). SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors. Nat Commun. 2023 Oct 23;14(1):6725. doi: 10.1038/s41467-023-42430-z. PMID: 37872153. https://pubmed.ncbi.nlm.nih.gov/37872153/
168. Arora S, Yang J, Akiyama T, James DQ, Morrissey A, Blanda T, Badjatia N, Lai WKM, Ko MSH, Pugh BF, Mahony S (2023). Joint sequence & chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin. bioRxiv. 2023 Oct 31:2023.10.06.561228. doi: 10.1101/2023.10.06.561228. Preprint. PMID: 37873361. https://pubmed.ncbi.nlm.nih.gov/37873361/
169. Koseki T, Teramachi M, Koga M, Ko MSH, Amano T, Yu H, Amano M, Leyder E, Badiola M, Ray P, Kim J, Ko AC, Achour A, Weng NP, Imai T, Yoshida H, Taniuchi S, Shintani A, Fujigaki H, Kondo M, Doi Y (2023). A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2. Vaccines (Basel). 11(12):1767. https://pubmed.ncbi.nlm.nih.gov/38140172/
*170. Akiyama T, Ishiguro KI, Chikazawa N, Ko SBH, Yukawa M, Ko MSH (2024). ZSCAN4-binding motif-TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes. DNA Res. 31(1):dsad029. https://pubmed.ncbi.nlm.nih.gov/38153767/
*171. Myers KC, Davies SM, Lutzko C, Wahle R, Grier DD, Aubert G, Norris K, Baird DM, Koga M, Ko AC, Amano T, Amano M, Yu H, Ko MSH (2025). Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells. NEJM Evid. 4(3):EVIDoa2400252. https://pubmed.ncbi.nlm.nih.gov/39998303/
172. Morita A, Ishii M, Asakura T, Yotsukura M, Hegab AE, Kusumoto T, Namkoong H, Ogawa T, Nakatake Y, Oda M, Saito F, Kamata H, Hamamoto J, Okamori S, Ebisudani T, Yasuda H, Sugimoto S, Kuze Y, Seki M, Suzuki Y, Hasegawa N, Asamura H, Watanabe H, Ko M, Sato T, Ieda M, Fukunaga K (2025). Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells. NPJ Regen Med. 10(1):30. https://pubmed.ncbi.nlm.nih.gov/40550799/
173. Kusumoto T, Yotsukura M, Asakura T, Namkoong H, Ogawa T, Hegab AE, Nakatake Y, Oda M, Saito F, Kamata H, Hamamoto J, Okamori S, Seki M, Suzuki Y, Hasegawa N, Asamura H, Watanabe H, Ko MSH, Ieda M, Fukunaga K, Ishii M (2025). Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice. Biochem Biophys Res Commun. 778:152384. https://pubmed.ncbi.nlm.nih.gov/40700809/
174. Akiyama T, Nakahara T, Sato S, Ishiguro KI, Yukawa M, Yamamoto M, Takahashi H, Ko MSH (2026). Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency. Development. 2026 Mar 30:dev.205328.
https://pubmed.ncbi.nlm.nih.gov/41906541/
● Book Chapters
B1. Takano T, and Ko MSH. Enhancer sequences for gene expression regulation. In: Takano, T. (Ed.): Introduction to Genetic Engineering. Tokyo, Nanzan-Doh, Press, 1985, pp. 227-256 (in Japanese).
B2. Ko MSH. An equalized cDNA library and its application. Protein, nucleic acid and enzyme. 38: 420-428, 1993 (in Japanese).
B3. Ko MSH.: Strategy for the construction of an equalized cDNA library. In: Nojima, Y. (Ed.): Gene Libraries, Tokyo, Yoh-Do Sha, Press, 1994, pp. 135-144 (in Japanese).
B4. Ko M SH. Equalized cDNA libraries. In: Larrick, J.W., and Siebert, P.D. (Eds): Reverse Transcriptase PCR. London, Ellis Horwood, 1995, pp. 245-264.
B5. Kimber WL, Piao Y, Tanaka TS, Yoshikawa T, Hamatani T, Carter MG, and Ko MSH. Systematic Analysis of Mouse Preimplantation Development. In: Watson, A. (Ed): Mammalian Embryo Genomics: Biological Resource Management in Agriculture. Paris, OECD (Organization for Economic Co-Operation and Development), 2003, pp. 37-46.
B6. Tanaka TS, Carter MG, Aiba K, Jaradat SA, and Ko MSH. Genomic approaches to stem cell biology. In: Odorico, J.S., Pederson, R.A., and Zhang, S.U. (Eds): Human Pluripotent Stem Cells. New York, BIOS Scientific Publishers, Ltd, 2004, pp. 339-361.
B7. VanBuren V, and Ko MSH. Principles and Application of Embryogenomics. In: Meyers, R.A. (Ed.): Encyclopedia of Molecular Cell Biology and Molecular Medicine, 2nd Edition. Weinheim, WILEY-VCH, 2004, pp. 529-555.
B8. VanBuren V, and Ko MSH. Regulation of genome activity and genetic networks in mammals. In: Ruvinsky, A., and Graves, J.M. (Eds): Mammalian Genomics. Cambridge, CABI Publishing, 2004, pp. 201-220.
B9. Ko MSH (2008). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 17th Edition. (Eds. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J). McGraw-Hill, NY.
B10. Ko MSH (2011). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 18th Edition. (Eds. Longo DL, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Jameson JL, Loscalzo J). McGraw-Hill, NY.
B11. Ko MSH (2015). Stem Cell Biology. Harrison’s Principles of Internal Medicine, 19th Edition. (Eds. Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J). McGraw Hill Professional, NY.
日本語総説など(抜粋)
1. 洪 実(1985)。遺伝子の発現調節と細胞の分化。「遺伝子工学入門-組み換えDNA実験は何を明らかにしたかー 高野 利也編著」南山堂。第7章 7-8(pp. 249-256)
2. 洪 実(1993)。 均一化cDNAライブラリーとその応用。蛋白質核酸酵素 Vol.38, No. 3. (pp. 420-428)
3. 洪 実(1994)。 均一化cDNAライブラリーの作製法。「実験医学別冊バイオマニュアルシリーズ2、遺伝子ライブラリーの作製法。野島博編集」。羊土社。(pp. 135-144)
4. 洪 実(2001)。マウスの発生ゲノム学。「ポストシークエンスのゲノム科学4。ゲノムから個体へ 生命システムの理解に向けて 榊 佳之 (著, 編集), 小原 雄治 (編集)」中山書店。(pp. 135-146)
5. 中武 悠樹, 西山 晃, 洪 実(2012)。転写調節因子を自在に誘導できるES細胞バンクの作製とその応用。「再生医療を実現化する幹細胞のメディカルサイエンスstemnessと分化の制御、新規因子の発見から三次元組織形成など臨床につながる最新成果まで」実験医学 (0288-5514)30巻10号 Page1639-1645 (2012.06)
6. 洪 実(2013)。発生のシステム生物学と再生医療。発達腎研究会誌 (0919-7532) 21巻1号、 Page2-6 (2013.04)
7. 洪 繁、洪 実 (2013)。膵臓の組織修復と組織幹細胞。「実験医学増刊 臓器円環による恒常性の維持・変容・破綻」実験医学 2013.3、羊土社。
8. 天野 朋和, 洪 実(2014)。Zscan4によるテロメア維持と4倍体補完能の回復。「iPS細胞/ES細胞の生物学」遺伝: 生物の科学 (0387-0022)68巻1号 Page50-57(2014.01)。
9. 平田 哲也, 天野 朋和, 大須賀 穣, 洪 実(2014)。着床前期胚特異的遺伝子Zscan4と多能性幹細胞。産科と婦人科 (0386-9792)81巻3号 Page309-316(2014.03)。
10. 秋山 智彦, 洪 繁, 洪 実(2014)。着床前期胚、生殖細胞、幹細胞にかかわるZSCAN4。「生殖細胞-全能性を獲得し、世代を紡ぐサイクル」実験医学 (0288-5514)32巻6号 Page870-876(2014.04)。
11. 洪 実(2014)。幹細胞を維持する遺伝子ZSCAN4の発見。「血管!発見!物語」Vascular Medicine (1880-2478)10巻1号 Page77-81(2014.04)。
12. 洪 実(2014)。産婦人科臨床医のためのシステム生物学入門。「オミックスデータからみた婦人科疾患と遺伝情報の解釈-システム生物学の理解を通した婦人科腫瘍学の新展開」産科と婦人科 (0386-9792)81巻6号 Page689-693(2014.06)。
13. 山水 康平, 中武 悠樹, 洪 繁, 洪 実(2015)。分化誘導と分化転換転写因子を用いた多能性幹細胞から任意細胞への分化誘導法の開発。「再生医療2015幹細胞と疾患iPS細胞の研究最前線」実験医学 (0288-5514)33巻2号 Page239-246(2015.02)。
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マウス着床前胚の全遺伝子発現パターン

確率的に起こる遺伝子発現

マウスES細胞で2-5%の細胞で一過性に起こるZ4事象

確率的に起こる遺伝子発現のシミュレーションに使ったオートマトンモデル