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Elucidation of the mechanism of global gene expression repression in pluripotent stem cells

Research Project

Project/Area Number 20K16149
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Tada Yuhki  国立研究開発法人理化学研究所, バイオリソース研究センター, 開発研究員 (10746382)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsシングルセルRNA-seq / 多能性幹細胞 / 分化 / 転写 / 遺伝子発現 / ノックアウトマウス / scRNA-Seq / RNAポリメラーゼII
Outline of Research at the Start

申請者はシングルセルRNA-Seq解析により、多能性幹細胞の遷移過程においてグローバルな遺伝子発現抑制現象を観測した。さらに、この現象がランダム型X染色体不活性化の開始に関連する可能性を示している。しかし、この現象の発生機序や生物学的意義は依然として不明である。そこで、変動遺伝子解析により見出した候補分子に着目し、多能性幹細胞におけるグローバルな遺伝子発現抑制機構の解明を目指す。

Outline of Final Research Achievements

The applicants observed a global suppression of gene expression during pluripotent stem cell transition using single-cell RNA sequencing analysis. However, the mechanism and biological significance of this phenomenon remain unclear. Therefore, we conducted RNA velocity analysis to estimate the direction of state change of each single cell and analysis of knockout mice for the candidate molecule found by differential gene expression analysis. The results suggested that the global suppression of gene expression may be a turning point in the state transition of pluripotent stem cells, and that knockout of the molecule specifically up-regulated at that time may affect post-implantation embryonic development and lead to embryonic lethality.

Academic Significance and Societal Importance of the Research Achievements

グローバルな遺伝子発現抑制機構としていくつかの現象が知られている。代表例として、メスの胚におけるX染色体不活性化、オスの精子形成過程における減数分裂期性染色体不活性化、始原生殖細胞におけるRNAポリメラーゼII依存性の転写抑制が挙げられる。これらの現象の破綻は胎生致死や不妊などの様々な異常の原因となる。したがって、グローバルな遺伝子発現の抑制は個体発生に重要な意義を持つと考えられる。申請者は新規のグローバルな遺伝子発現抑制現象を多能性幹細胞の分化遷移過程に見出し、その作用機序に関与する可能性のある候補分子を同定し、機能解析の結果、この分子が発生に重要な役割を持つことを示すことに成功した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2020

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

  • [Journal Article] Universal surface biotinylation: A simple, versatile and cost-effective sample multiplexing method for single-cell RNA-seq analysis2022

    • Author(s)
      Sugimoto M, Tada Y, Shichino S, Koyamasu S, Tsumaki N, Abe K
    • Journal Title

      DNA Res

      Volume: 29 Issue: 3

    • DOI

      10.1093/dnares/dsac017

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell transcriptomics, scRNA-Seq and C1 CAGE discovered distinct phases of pluripotency during naive-to-primed conversion in mice2020

    • Author(s)
      Michael Bottcher, Yuhki Tada, Jonathan Moody, Masayo Kondo, Hiroki Ura, Imad Abugessaisa, Takeya Kasukawa, Chung-Chau Hon, Koji Nagao, Piero Carninci, Kuniya Abe
    • Journal Title

      bioRxiv

      Volume: 313239 Pages: 313239-313239

    • DOI

      10.1101/2020.09.25.313239

    • Related Report
      2020 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Two pre-primed pluripotent states emerged in naive-to-primed conversion process discovered by single cell analyses2023

    • Author(s)
      Yuhki Tada, Michael Bottcher, Hiroki Ura, Michihiko Sugimoto, Imad Abugessaisa, Takeya Kasukawa, Koji Nagao, Piero Carninci, Kuniya Abe
    • Organizer
      36th International Mammalian Genome Conference (IMGC2023)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Universal Surface Biotinylation (USB): A simple, versatile and cost-effective sample multiplexing method for single-cell RNA-seq analysis2022

    • Author(s)
      Yuhki Tada, Michihiko Sugimoto, Shigeyuki Shichino, Saeko Koyamatsu, Noriyuki Tsumaki, Kuniya Abe
    • Organizer
      シングルセルゲノミクス研究会2022
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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