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Genome Maintenance Mechanisms in Pluropotent Stem Cells

Research Project

Project/Area Number 16K07382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionNational Institute for Basic Biology

Principal Investigator

Tsubouchi Tomomi  基礎生物学研究所, 幹細胞生物学研究室, 准教授 (70754505)

Project Period (FY) 2016-04-01 – 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 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords胚性幹細胞 / ゲノム恒常性 / DNA複製 / dNTP / ES細胞 / dNTP産生 / DNA 複製 / dNTP産生 / 多能性幹細胞 / 幹細胞
Outline of Final Research Achievements

Embryonic stem cells are the stem cells that are established from an early stage of a developing embryo. ES cells are the origin of cell types of several hundreds that compose our bodies, and they are known to hold properties that are unique in various aspects of cell division cycle. During this research period, we found that replication machinery progress slowly at all stage of DNA replication (S) phase, and found that this is due to reduced amount of dNTPs. Despite the slow replication-machinery, ES cells complete DNA synthesis within similar amount of time compared to MEFs. Our results show that this is due to denser distribution of active DNA replication machinery along the genome.

Academic Significance and Societal Importance of the Research Achievements

ES細胞を含む多能性幹細胞は、体を構成する数百種類の細胞種を生み出す能力を持ち、再生医療への応用が期待されている。しかしながら生物体内では個体発生のごく初期に短期間にのみ存在する細胞群であり、ES細胞そのものの理解は不完全である。本研究ではES細胞のDNA複製制御に着目し、1) ES細胞が特有のDNA複製制御を持ち、ゲノム全体のDNA複製が時間内に確実に終了するよう制御されていること 2) ES細胞特異的なDNA複製制御には細胞内で合成されるdNTP量が他の細胞種と比較して低く維持されていること を明らかにした。本研究よりES細胞の維持にdNTP量が重要なファクターであることが明らかになった。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 Other

All Int'l Joint Research (4 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results)

  • [Int'l Joint Research] サセックス大学(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2016 Research-status Report
  • [Presentation] Regulation of DNA replication in mammalian pluripotent stem cells2019

    • Author(s)
      Tomomi Tsubouchi
    • Organizer
      International Symposium for Female Researchers in Chromatin Biology 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A unique regulation of dNTP levels in mammalian pluripotent stem cells2019

    • Author(s)
      Yasunao Kamikawa, Akino Matsumoto and Tomomi Tsubouchi
    • Organizer
      Cold Spring Harbor Laboratory Meeting: Eukaryotic DNA Replicatin & Genome Maintenance
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞におけるdNTP産生制御とゲノム恒常性2019

    • Author(s)
      上川泰直、松本陽乃、坪内知美
    • Organizer
      第25回DNA複製・組換え・修復ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳類多能性幹細胞におけるDNA複製ストレスと複製制御2019

    • Author(s)
      上川泰直、長沼麻衣、坪内知美
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 哺乳類多能性幹細胞におけるDNA複製制御2019

    • Author(s)
      坪内知美
    • Organizer
      第37回染色体ワークショップ/ 第18回核ダイナミクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Unique regulation of dNTP production in mammalian pluripotent stem cells2018

    • Author(s)
      上川泰直 坪内知美
    • Organizer
      EMBO workshop on DNA Replication, Chromosome Segregation and Fate Decisions
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞におけるDNA複製ストレス応答2018

    • Author(s)
      上川泰直 坪内知美
    • Organizer
      第90回日本遺伝学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 多能性幹細胞におけるDNA複製完了のメカニズム2018

    • Author(s)
      上川泰直 坪内知美
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 複製フォーク動態を介した多能性幹細胞におけるゲノム安定性維持機構2018

    • Author(s)
      上川泰直 坪内知美
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 多能性細胞におけるゲノム恒常性維持機構(仮題)2018

    • Author(s)
      坪内知美
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 多能性細胞の複製ストレス応答機構(仮題)2018

    • Author(s)
      上川泰直 坪内知美
    • Organizer
      日本遺伝学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Genome maintenance mechanisms in mammalian pluripotent stem cells2017

    • Author(s)
      坪内知美
    • Organizer
      第59回日本植物生理学会年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] DNA replication and genome stability in pluripotent stem cells2017

    • Author(s)
      坪内知美
    • Organizer
      2017年度生命科学系合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2024-12-25  

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