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Spatially and time-dependent analysis of initial phase of epigenetic regulation in X chromosome reactivation

Research Project

Project/Area Number 16K07244
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionUniversity of Tsukuba

Principal Investigator

Nishimura Ken  筑波大学, 医学医療系, 准教授 (80500610)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsiPS細胞 / X染色体 / エピジェネティクス / SNP / 再活性化 / 3S reprogramming system
Outline of Final Research Achievements

When we produce iPS cells, a transcription of RNA from an inactivated X chromosome is induced. And the induction is insufficient in a partially-reprogrammed iPS cells. Thus, we tried to find regions from which the X chromosome reactivation starts and investigate a mechanism to produce well-reprogrammed iPS cells. We succeeded to develop SNP cDNA typing system which can determine the X chromosome reactivation and, by using the system, isolate iPS cells with different reactivation state. A transcriptional profile in the iPS cells made us identify the initiation regions of the X chromosome reactivation.

Academic Significance and Societal Importance of the Research Achievements

本研究成果を元に、X染色体の再活性化を引き起こす分子の同定を始めとして、X染色体再活性化の分子機構解析が進むと考えられる。そしてその知見を生かして、iPS細胞誘導時にX染色体再活性化を効率良く引き起こすことが可能になり、最終的に、高い多能性を獲得した高品質iPS細胞を効率良く誘導する方法の確立につながることが期待される。このような技術は、iPS細胞を用いた再生医療の実用化に大きく貢献すると考えられることから、大きな学術的、社会的意義があると思われる。

Report

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

    (16 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 5 results) Remarks (1 results)

  • [Journal Article] Live-cell imaging of subcellular structures for quantitative evaluation of pluripotent stem cells2019

    • Author(s)
      Nishimura Ken、Ishiwata Hiroshi、Sakuragi Yuta、Hayashi Yohei、Fukuda Aya、Hisatake Koji
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1777-1777

    • DOI

      10.1038/s41598-018-37779-x

    • NAID

      120007128201

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tcl1による代謝リプログラミングがiPS細胞誘導を促進する2018

    • Author(s)
      西村健、久武幸司
    • Journal Title

      医学のあゆみ

      Volume: 265 Pages: 293-294

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Live cell imaging of X chromosome reactivation during somatic cell reprogramming2018

    • Author(s)
      Tran Thi Hai Yen、Fukuda Aya、Aizawa Shiho、Bui Phuong Linh、Hayashi Yohei、Nishimura Ken、Hisatake Koji
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 15 Pages: 86-92

    • DOI

      10.1016/j.bbrep.2018.07.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time-course transcriptome analysis of human cellular reprogramming from multiple cell types reveals the drastic change occurs between the mid phase and the late phase2018

    • Author(s)
      Kuno Akihiro、Nishimura Ken、Takahashi Satoru
    • Journal Title

      BMC Genetics

      Volume: 19 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s12864-017-4389-8

    • NAID

      120007134583

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simple and effective generation of transgene-free induced pluripotent stem cells using an auto-erasable Sendai virus vector responding to microRNA-3022017

    • Author(s)
      Nishimura Ken、Ohtaka Manami、Takada Hitomi、Kurisaki Akira、Tran Nhi Vo Kieu、Tran Yen Thi Hai、Hisatake Koji、Sano Masayuki、Nakanishi Mahito
    • Journal Title

      Stem Cell Research

      Volume: 23 Pages: 13-19

    • DOI

      10.1016/j.scr.2017.06.011

    • NAID

      120007134806

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A role for KLF4 in promoting the metabolic shift via TCL1 during induced pluripotent stem cell generation.2017

    • Author(s)
      Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Tran YTH, Bui PL, Borisova E, Sakuragi Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K
    • Journal Title

      Stem Cell Reports

      Volume: 8 Issue: 3 Pages: 787-801

    • DOI

      10.1016/j.stemcr.2017.01.026

    • NAID

      120007129229

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Quantitative Assessment of Pluripotent Stem Cells by an Improved RM-DIC Imaging System2018

    • Author(s)
      Nishimura K, Ishiwata H, Sakuragi Y, Hayashi Y, Fukuda A, Hisatake K
    • Organizer
      2018 TERMIS World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] KLF4-dose dependent metabolic shift through TCL1 during iPSC generation2018

    • Author(s)
      Nishimura K, Kumar BA, Hayashi Y, Fukuda A, Hisatake K
    • Organizer
      ISSCR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanistic analysis of the initiation of retroviral gene silencing by reprogramming factors2018

    • Author(s)
      Bui PL、Nishimura K、Hisatake K
    • Organizer
      The Exploring identity: lessons from genomes and epigenomes meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] X染色体の再活性化をモデルとしたエピジェネティクス転写制御機構の解明2018

    • Author(s)
      相澤志穂、Bui PL、西村健、久武幸司
    • Organizer
      超異分野学会2018
    • Related Report
      2017 Research-status Report
  • [Presentation] iPS細胞誘導機構解明のためのX染色体再活性化状態定量システムの開発2017

    • Author(s)
      相澤志穂、Bui PL、西村健、久武幸司
    • Organizer
      第16回日本再生医療学会
    • Place of Presentation
      仙台国際センター・宮城県・仙台市
    • Year and Date
      2017-03-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanistic analysis of the initiation of retroviral gene silencing by reprogramming factors2017

    • Author(s)
      Bui PL, Nishimura K, Hisatake K
    • Organizer
      The 6th Human Biology Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] iPS細胞誘導におけるX染色体再活性化機構の解析2017

    • Author(s)
      相澤志穂、Bui PL、西村健、久武幸司
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] iPS細胞誘導におけるX染色体再活性化を定量化する方法の開発2016

    • Author(s)
      相澤志穂、Bui PL、西村健、久武幸司
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜・神奈川県・横浜市
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] A quantitative method for analysis of X chromosome reactivation in iPSC production2016

    • Author(s)
      Aizawa S, Bui PL, Nishimura K, Hisatake K
    • Organizer
      The 5th Human Biology Symposium
    • Place of Presentation
      つくば国際会議場・茨城県・つくば市
    • Year and Date
      2016-09-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] iPS 細胞の品質管理を迅速かつ簡便に行える顕微鏡システムの開発

    • URL

      http://www.tsukuba.ac.jp/attention-research/p201902121500.html

    • Related Report
      2018 Annual Research Report

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

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