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Reprogramming associated point mutations and ROS

Research Project

Project/Area Number 17H03615
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical genome science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

ARAKI RYOKO  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, グループリーダー(定常) (40392211)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywordsゲノム初期化 / 変異 / iPS細胞 / 全ゲノムシーケンシング / ゲノムリプログラミング / 点突然変異 / 活性酸素 / ゲノム変異 / リプログラミング / 酸化ストレス / ゲノム / 再生医学
Outline of Final Research Achievements

Thus far, presence of a significant number of mutations has been reported in iPS cell genomes. In this study, we aimed to understand the mechanism which causes these numerous mutations and develop a method to generate iPS cells with few mutations. In this study, we demonstrated that the initial stage of genome reprogramming is radio resistance. Further analyses revealed a overexpression of CyclinD1 and a deficiency of cell cycle check point function occur in a transient manner during the initial stage of genome reprogramming. Importantly, it was showed that the point mutations in iPS cell genomes accumulate just in the initial stage. In addition, we here also discovered that iPS cells established from human cord blood-derived erythroblasts had a mutation frequency of 1/5 to 1/10 of the frequency observed in previous iPS cells.

Academic Significance and Societal Importance of the Research Achievements

ゲノム初期化のメカニズムの理解、更にiPS細胞を用いた再生医療研究への貢献が期待される。

Report

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

    (8 results)

All 2020 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency2020

    • Author(s)
      Araki Ryoko、Hoki Yuko、Suga Tomo、Obara Chizuka、Sunayama Misato、Imadome Kaori、Fujita Mayumi、Kamimura Satoshi、Nakamura Miki、Wakayama Sayaka、Nagy Andras、Wakayama Teruhiko、Abe Masumi
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 197-197

    • DOI

      10.1038/s41467-019-13830-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hotspots of De Novo Point Mutations in Induced Pluripotent Stem Cells2017

    • Author(s)
      Yoshihara Masahito、Araki Ryoko、Kasama Yasuji、Sunayama Misato、Abe Masumi、Nishida Kohji、Kawaji Hideya、Hayashizaki Yoshihide、Murakawa Yasuhiro
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 2 Pages: 308-315

    • DOI

      10.1016/j.celrep.2017.09.060

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Reprogrammed cellゲノムにおけるINDEL変異解析2019

    • Author(s)
      上村 悟氏, 菅 智, 砂山 美里, 藤森(法喜)ゆう子, 小原 千寿香, 今留 香織, 藤田 真由美, 中村 美樹, 安倍 真澄, 荒木 良子
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] iPS細胞におけるゲノム変異 -INDEL解析-2018

    • Author(s)
      菅 智, 砂山 美里, 藤森(法喜) ゆう子, 小原 千寿香, 今留 香織, 藤田 真由美, 中村 美樹, 安倍 真澄, 荒木 良子
    • Organizer
      第41回 日本分子生物学会年会, 日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] iPS細胞における点突然変異2018

    • Author(s)
      荒木 良子
    • Organizer
      Kofu Stem Cell Conference 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゲノム初期化多能性幹細胞コロニーに観られる点突然変異不均一性のin-depth解析2017

    • Author(s)
      砂山 美里, 藤森 ゆう子, 菅 智, 小原 千寿香, 今留 香織, 荒木 良子, 安倍 真澄
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞ゲノム内点突然変異の頻度は変えられるか?2017

    • Author(s)
      藤森 ゆう子, 砂山 美里, 小原 千寿香, 今留 香織, 菅 智, 藤田 真由美, 安倍 真澄, 荒木 良子
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 誘導多能性幹細胞を製造する方法、誘導多能性幹細胞樹立過程における点変異を抑制する方法、及び誘導多能性幹細胞2019

    • Inventor(s)
      荒木良子、小原千寿香、藤森ゆう子、安倍真澄
    • Industrial Property Rights Holder
      量子科学技術研究開発機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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

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