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Molecular mechanism of interference with iPSC induction

Research Project

Project/Area Number 24615004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Regenerative medicine
Research InstitutionKyoto University

Principal Investigator

MASUI Shinji  京都大学, iPS細胞研究所, 講師 (20342850)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsiPS細胞 / マスター転写因子 / ポリコーム / コアネットワーク / ES細胞 / 転写因子 / 初期化 / ダイレクトリプログラミング
Outline of Final Research Achievements

We have previously shown that master transcription factors tend to interfere with dedifferentiation triggered by iPSC induction technique in a given cell type. In this study we sought to elucidate the mechanism of the interference. Overexpression of Yamanaka factors including Oct3/4 repressed genes highly expressed in somatic cells. This repression was thought to be their direct effect, as chromatin immunoprecipitation indicated direct binding of Oct3/4 on genes highly expressed in somatic cells. On the other hand, overexpression of a master transcription factor in somatic cells during iPSC induction inhibited this repression and decreased iPSC induction efficiency. These data indicate that this repression is necessary for iPSC induction, and that the interference can be seen as the antagonism between Yamanaka factors and master transcription factors on genes highly expressed in somatic cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2014 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles.2013

    • Author(s)
      Hikichi T, Matoba R, Ikeda T, Watanabe A, Yamamoto T, Yoshitake S, Tamura-Nakano M, Kimura T, Kamon M, Shimura M, Kawakami K, Okuda A, Okochi H, Inoue T, Suzuki A, Masui S.
    • Journal Title

      Proceeding of the National Academy of Sciences of USA

      Volume: 110 Issue: 16 Pages: 6412-6417

    • DOI

      10.1073/pnas.1220200110

    • NAID

      120005244176

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles2014

    • Author(s)
      Masui S
    • Organizer
      47th Annual Meeting for the Japanese Society of Developmental Biologists (JSDB) cosponsored by the Asia-Pacific Developmental Biology Network (APDBN)
    • Place of Presentation
      名古屋市
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] 初期化を阻害する因子が分化を促進する2014

    • Author(s)
      升井 伸治
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      国立京都国際会館、京都市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles2013

    • Author(s)
      Shinji Masui
    • Organizer
      ISSCR 10th annual meeting
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 初期化を阻害する因子が分化を促進する2013

    • Author(s)
      升井 伸治
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド、神戸市
    • Related Report
      2013 Research-status Report
  • [Remarks] 京都大学iPS細胞研究所 CiRA(サイラ)

    • URL

      http://www.cira.kyoto-u.ac.jp/j/index.html

    • Related Report
      2012 Research-status Report
  • [Remarks] 升井研究室

    • URL

      http://www.cira.kyoto-u.ac.jp/masui/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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