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Exporing role of cell-cell communication in human embryonic stem cells

Research Project

Project/Area Number 17K07395
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionKyoto University

Principal Investigator

Ohgushi Masatoshi  京都大学, ウイルス・再生医科学研究所, 准教授 (00462664)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsヒトES細胞 / 多能性 / 細胞間接着 / セマフォリン / ゲノム編集 / シグナル伝達 / ヒト多能性幹細胞 / 細胞間コミュニケーション
Outline of Final Research Achievements

In this research, I aim to explore roles of semaphori-6A, a signaling molecule implicated in axon guidance, in human embryonic stem cell (hESC) biology. For this end, I try to develop a conditional gene knockout system using a Crispr-cas9 genome editing tool.
Following the improved strategy, I established some hESC lines in which 2nd exon of SEME6A gene were flowed. I confirmed that lentivirus-mediated introduction of Cre recombinase induced deletion of 2nd exon and the expression semaphoring-6A protein decreased to the undetectable level. Preliminary data suggested that SAMA6A gene-disrupted hESCs show some abnormal phenotypes. This experimental platform allows us to genetically explore the function of a given gene that plays essential role in hESCs.

Academic Significance and Societal Importance of the Research Achievements

ES/iPS細胞を用いた新たな医療・創薬への期待を背景として、様々な細胞を分化誘導する研究が世界中で活発に行われている。しかしながら、それらの学術成果の実用化を見据えた場合、分化誘導手法の再現性、細胞株間での性質のばらつき、そして原材料である多能性幹細胞培養の不安定さ(頻繁な細胞死や自発分化)など、品質と汎用性を担保した大規模細胞調製を達成するための課題は山積している。幹細胞研究の成果を多くの国民に届けるために、セマフォリンシグナルを介した細胞間コミュニケーションの実体解明を進め、多能性幹細胞の高品質化を達成したい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017

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

  • [Journal Article] A Practical Protocol for the Conditional Depletion of Rho Isoforms in Human Embryonic Stem Cells.2018

    • Author(s)
      Ohgushi Masatoshi
    • Journal Title

      Methods in Molecular Biology

      Volume: 1821 Pages: 283-295

    • DOI

      10.1007/978-1-4939-8612-5_20

    • ISBN
      9781493986118, 9781493986125
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells2017

    • Author(s)
      Ohgushi Masatoshi、Minaguchi Maki、Eiraku Mototsugu、Sasai Yoshiki
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 1 Pages: 58-66

    • DOI

      10.1016/j.stemcr.2017.05.003

    • NAID

      120006325118

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Characterization of the progenitor cell state during ESC-to-trophoblast differentiation2019

    • Author(s)
      Masatoshi Ohgushi
    • Organizer
      第17回幹細胞シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells.2018

    • Author(s)
      Masatoshi Ohgushi
    • Organizer
      ISSCR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Intrinsic genetic program that drives trophoblast differentiation from human ES cells2018

    • Author(s)
      Masatoshi Ohgushi
    • Organizer
      第16回幹細胞シンポジウム
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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