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Chromosome stability by Rho-family small GTPase regulator in human embryonic stem cells

Research Project

Project/Area Number 26830088
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Masatoshi Ohgushi  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 上級研究員 (00462664)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsヒトES細胞 / 染色体安定性 / Rhoシグナル経路 / 多能性幹細胞 / ゲノム不安定性 / ヒト多能性幹細胞 / 異数染色体
Outline of Final Research Achievements

Human pluripotent stem cells, including embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), hold huge potential as reproductive resources for cell-therapies to treat a variety of diseases as well as for drug discovery. In this study, we explored biological function of ABR, a regulator of Rho-family small GTPases, in hESCs. We found that RNAi-mediated depletion of ABR caused several defects in mitotic process, leading to anueploidy transformation with a high frequency. This indicates that ABR has a pivotal role in mitotic fidelity and precise inheritance of genetic information in self-renewing hESCs. Since the emergence of genetically detrimental cells during long-term culture has been regarded to be a big obstacle for the practical utilization of hESCs/iPSCs, these results provide implications for developing hESC/iPSC culture methods that are better suited for human genetic studies and cell-based therapies.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 Other

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

  • [Journal Article] A RHO small GTPase regulator ABR secures mitotic fidelity in human embryonic stem cells2017

    • Author(s)
      大串雅俊, 水口真希, 永樂元次, 笹井芳樹
    • Journal Title

      Stem Cell Reports

      Volume: 印刷中

    • NAID

      120006325118

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Generation of functional hippocampal neurons from self-organizing human ES cell-derived dorsomedial telencephalic tissue.2016

    • Author(s)
      坂口英哉、門嶋大輔、宗園美香、成井信博、石田義人、大串雅俊、高橋淳、永樂元次、笹井芳樹
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 10351-10351

    • DOI

      10.1038/ncomms9896

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rho-signaling-directed YAP/TAZ activity underlies the long-term survival and expansion of human embryonic stem cells.2015

    • Author(s)
      大串雅俊、水口真希、笹井芳樹
    • Journal Title

      Cell Stem Cell

      Volume: 17 Issue: 4 Pages: 448-461

    • DOI

      10.1016/j.stem.2015.07.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Toward understanding the immortal trait of human embryonic stem cells2016

    • Author(s)
      大串雅俊
    • Organizer
      第14回 幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-05-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Toward understanding the immortal trait of human embryonic stem cells2016

    • Author(s)
      大串雅俊
    • Organizer
      第14回幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒトES細胞の不死性を支える生存メカニズム2016

    • Author(s)
      大串雅俊
    • Organizer
      第15回日本再生医療学会年会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] Rhoシグナル伝達経路による転写共役因子YAP及びTAZの活性化はヒトES細胞の維持培養に必要である

    • URL

      http://first.lifesciencedb.jp/archives/11658

    • Related Report
      2015 Research-status Report
  • [Remarks] 「不死」のES細胞…増え続け、生き続ける不思議

    • URL

      http://www.sankei.com/west/news/150926/wst1509260003-n1.html

    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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