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体細胞初期化過程におけるゲノムインプリンティング安定性の検討

Research Project

Project/Area Number 15J05792
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Experimental pathology
Research InstitutionKyoto University

Principal Investigator

八木 正樹  京都大学, 医学研究科, 特別研究員(DC1)

Project Period (FY) 2015-04-24 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2017: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2016: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2015: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsES細胞 / iPS細胞 / DNAメチル化 / ゲノムインプリンティング / 個体発生能 / iPS細胞品質評価 / 多能性幹細胞 / 品質評価
Outline of Annual Research Achievements

多能性幹細胞、発生過程および疾患におけるエピゲノム制御に興味を持ち、研究を行っている。博士論文研究では、汎用的に用いられている幹細胞培養法がマウスES細胞のエピゲノム状態、特に発生に重要なゲノムインプリントに影響を与え、インプリントを失ったES細胞は個体発生能が低下することを明らかにした。さらには、それら問題を解決するための新規培養法を見出し、より高品質なES細胞を効率良く樹立することに成功した。この成果(申請者の学位論文)は2017年7月にNature誌に掲載された。同成果はNature誌「News & Views」トピックでも取り上げられた。インプリントが多能性幹細胞の品質に重要であることから、iPS細胞誘導過程におけるインプリント領域の安定性も解析している。初期化過程で安定的な領域とメチル化の変動が起こりやすい不安的な領域が存在することを発見しており、さらには安定的なインプリントを有するiPS細胞の樹立方法を同定した。また、マウスとヒトの多能性幹細胞においてインプリント異常が生じやすい領域は比較的共通しており、それら領域は様々ながんにおいても異常なメチル化状態として観察されることがわかった。以上のことから、本研究成果は多能性幹細胞の品質評価につながることが期待され、より高品質なiPS細胞の樹立にも発展するのではないかと考えられる。現在本研究成果は論文投稿中(筆頭著者としての論文)である。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (20 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 3 results) Book (2 results)

  • [Journal Article] Epigenetic foundations of pluripotent stem cells that recapitulate in vivo pluripotency2017

    • Author(s)
      Yagi Masaki、Yamanaka Shinya、Yamada Yasuhiro
    • Journal Title

      Laboratory Investigation

      Volume: 97 Issue: 10 Pages: 1133-1141

    • DOI

      10.1038/labinvest.2017.87

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation2017

    • Author(s)
      Yagi M, Kishigami S, Tanaka A, Semi K, Mizutani E, Wakayama S, Wakayama T, Yamamoto T, Yamada Y.
    • Journal Title

      Nature

      Volume: 548 Issue: 7666 Pages: 224-227

    • DOI

      10.1038/nature23286

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.2017

    • Author(s)
      Hashimoto K, Yamada Y, Semi K, Yagi M, Tanaka A, Itakura F, Aoki H, Kunisada T, Woltjen K, Haga H, Sakai Y, Yamamoto T, *Yamada Y.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 4 Pages: 758-763

    • DOI

      10.1073/pnas.1614197114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation2017

    • Author(s)
      Masaki Yagi, Satoshi Kishigami, Akito Tanaka, Katsunori Semi, Eiji Mizutani, Sayaka Wakayama, Teruhiko Wakayama, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      先端モデル動物支援プラットフォーム成果報告会
    • Place of Presentation
      滋賀
    • Year and Date
      2017-02-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Epigenetic Variations at Imprinted Regions Are Dependent on Gene Loci and Pluripotent State2017

    • Author(s)
      Masaki Yagi, Akito Tanaka, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      ISSCR
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Derivation of ground state female ES cells maintaining gamete derived DNA methylation2017

    • Author(s)
      Masaki Yagi, Satoshi Kishigami, Akito Tanaka, Katsunori Semi, Eiji Mizutani, Sayaka Wakayama, Teruhiko Wakayama, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      CiRA International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stability of genomic imprints in naive and primed pluripotent stem cells derived from embryos and somatic cells2017

    • Author(s)
      Masaki Yagi, Akito Tanaka, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      CiRA International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Unique roles of de novo DNA methyltransferases in mammalian development2017

    • Author(s)
      Masaki Yagi, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      CiRA retreat
    • Related Report
      2017 Annual Research Report
  • [Presentation] Derivation of ground state female ES cells maintaining gamete derived DNA methylation2017

    • Author(s)
      Masaki Yagi, Satoshi Kishigami, Akito Tanaka, Katsunori Semi, Eiji Mizutani, Sayaka Wakayama, Teruhiko Wakayama, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      先端モデル動物支援プラットフォーム成果発表会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Opposing effects of ground state culture condition on ESC functional properties2016

    • Author(s)
      Masaki Yagi, Satoshi Kishigami, Akito Tanaka, Katsunori Semi, Eiji Mizutani, Sayaka Wakayama, Teruhiko Wakayama, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      CiRA retreat
    • Place of Presentation
      兵庫
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Epigenetic variations at imprinting control regions are dependent on clone and gene loci but not on pluripotent states2016

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      International Society for Stem Cell Research (ISSCR16)
    • Place of Presentation
      アメリカ合衆国(サンフランシスコ)
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Epigenetic variations at imprinting control regions are dependent on clone and gene loci but not on pluripotent states2016

    • Author(s)
      Masaki Yagi, Takuya Yamamoto, Yasuhiro Yamada
    • Organizer
      International Society for Stem Cell Research 2016
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2016-06-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analyses of DNA methylation at imprinting control regions during somatic cell reprogramming2016

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      CiRA/ISSCR 2016 International Symposia
    • Place of Presentation
      京都
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analyses of DNA methylation at imprinting control regions during somatic cell reprogramming2016

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      Epigenome Dynamics and Regulation in Germ Cells
    • Place of Presentation
      京都
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analyses of genomic imprinting in mouse pluripotent stem cells derived from F1 mice crossed between MSM/Ms and 129/Sv2015

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      モロシヌス研究会
    • Place of Presentation
      兵庫
    • Year and Date
      2015-07-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Epigenetic variations of imprinted genes in mouse pluripotent stem cells2015

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      International Society for Stem Cell Research (ISSCR15)
    • Place of Presentation
      スウェーデン(ストックホルム)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Clone and gene specific variations of genomic imprinting during iPS cell derivation2015

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      第9回エピジェネティクス研究会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Clone and gene specific variations of genomic imprinting during iPS cell derivation2015

    • Author(s)
      Masaki Yagi, Katsunori Semi, Akito Tanaka, Knut Woltjen, Shinya Yamanaka, and Yasuhiro Yamada
    • Organizer
      CiRAリトリート2015
    • Place of Presentation
      滋賀
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
  • [Book] 「がんとリプログラミング」2015

    • Author(s)
      八木 正樹、蝉 克憲、山田 泰広
    • Total Pages
      5
    • Publisher
      日本臨牀
    • Related Report
      2015 Annual Research Report
  • [Book] 「細胞初期化技術を用いたがんエピゲノム研究」2015

    • Author(s)
      八木 正樹、山田 泰広
    • Total Pages
      5
    • Publisher
      細胞工学
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-11-26   Modified: 2024-03-26  

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