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The study of cell competition in mouse development

Research Project

Project/Area Number 16K18550
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Developmental biology
Research InstitutionOsaka University

Principal Investigator

HASHIMOTO Masakazu  大阪大学, 生命機能研究科, 助教 (60580496)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords細胞競合 / Tead活性 / エピブラスト / ゲノム編集 / Hippoシグナル / 個体発生 / 細胞死
Outline of Final Research Achievements

The epiblast is a pluripotent cell population first formed in preimplantation embryos and its quality is important for proper development. In this study, we examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor Tead and its coactivator Yap regulate expression of pluripotency factors and cells showing low Tead activity are eliminated from the epiblast through cell competition. Cell competition functions as a safeguard against developmental fluctuations in pluripotency factor expression by Tead activity to ensure the production of an epiblast with naive pluripotency.

Academic Significance and Societal Importance of the Research Achievements

エピブラストはからだのほぼ全ての細胞の元となっているため、高く均質な多能性を有している必要があるが、その獲得機構はこれまであまり明らかにされてこなかった。本研究から、エピブラストが強固な多能性を獲得するメカニズムを見いだすことができた。着床前胚のエピブラストはin vitroにおけるES細胞やiPS細胞に相当するが、これらは多能性の状態が均質ではないことが現在の再生医療における問題点である。本研究成果によって ES細胞やiPS細胞の多能性を均質化する手法を開発できるかもしれない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016

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

  • [Journal Article] Electroporation of Cas9 protein/sgRNA into early pronuclear zygotes generates non-mosaic mutants in the mouse.2016

    • Author(s)
      Hashimoto M, Yamashita Y, Takemoto T.
    • Journal Title

      Developmental Biology

      Volume: 418 Issue: 1 Pages: 1-9

    • DOI

      10.1016/j.ydbio.2016.07.017

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Tead-Yap activity in inner cell mass promotes naive pluripotency and its variation triggers cell competition to establish high quality epiblast2018

    • Author(s)
      Masakazu Hashimoto
    • Organizer
      Joint Annual Meeting of 51st JSDB and 70th JSCB
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス着床前胚のエピブラストはTead/Yap活性依存的な選択的細胞死を経て多能性を均質化させる2017

    • Author(s)
      橋本昌和、竹之下憂祐、百合祐樹、佐々木洋
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] The Role of Tead activity-dependent cell competition in mouse early development2017

    • Author(s)
      Masakazu Hashimoto, Yusuke Takenoshita, Yuki Yuri, Hiroshi Sasaki
    • Organizer
      細胞競合国際シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス初期胚における細胞競合の解析2016

    • Author(s)
      橋本昌和、竹之下憂祐、百合祐樹、佐々木洋
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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