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Analysis of hematopoietic stem cell activation induced by Nrf2 inducers

Research Project

Project/Area Number 15K18999
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionTohoku University

Principal Investigator

MURAKAMI Shohei  東北大学, 加齢医学研究所, 産学官連携研究員 (20746911)

Research Collaborator SUZUKI Takuma  東北大学, 大学院・医学系研究科・血液・免疫病学分野, 大学院生
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsKeap1-Nrf2制御系 / 造血幹細胞 / 増殖・分化
Outline of Final Research Achievements

To examine whether a stress-responsive transcription factor, Nrf2, contributes to proliferation of hematopoietic stem cells (HSCs) by its transient activation, we treated mice with an Nrf2 inducer, CDDO-Im, and investigated the effects of transient Nrf2 activation on HSCs. Nrf2 activation induced by CDDO-Im treatment promoted HSC proliferation, but bone marrow transplantation experiment revealed that the proliferative HSCs due to the Nrf2 activation easily undergo differentiation and hardly maintain their stem activity. It turned out that under the culture condition with thrombopoietin (TPO), Nrf2 activation enhanced HSC differentiation into megakaryocyte-like cells. Therefore, Nrf2 activation likely induces proliferation/differentiation of HSCs through enhancing the sensitivity to TPO signaling.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] 血液・免疫細胞および白血病細胞におけるKEAP1-NRF2制御系の役割2016

    • Author(s)
      村上昌平、本橋ほづみ
    • Journal Title

      臨床血液

      Volume: 57 Pages: 1860-1868

    • NAID

      130005420735

    • Related Report
      2016 Annual Research Report
  • [Journal Article] NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea2016

    • Author(s)
      Honkura, Y. Matsuo, H. Murakami, S. Sakiyama, M. Mizutari, K. Shiotani, A. Yamamoto, M. Morita, I. Shinomiya, N. Kawase, T. Katori, Y. Motohashi, H.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 19329-19329

    • DOI

      10.1038/srep19329

    • NAID

      130005260938

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of Nrf2 in cell proliferation and differentiation2015

    • Author(s)
      Shohei Murakami and Hozumi Motohashi.
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 88 Pages: 168-178

    • DOI

      10.1016/j.freeradbiomed.2015.06.030

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 造血幹細胞におけるKEAP1-NRF2制御系の機能解析2016

    • Author(s)
      村上昌平
    • Organizer
      第89回 日本生化学大会
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス(宮城県・仙台)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Keap1-Nrf2制御系による造血幹細胞の増殖・老化制御2016

    • Author(s)
      村上昌平
    • Organizer
      新学術領域研究 酸素生物学&ダインイングコード
    • Place of Presentation
      一宮シーサイドオーツカ(千葉県・一宮市)
    • Year and Date
      2016-01-26
    • Related Report
      2015 Research-status Report
  • [Presentation] KEAP1-NRF2 system contributes to hematopoietic stem cell senescence2016

    • Author(s)
      村上昌平
    • Organizer
      老化シンポジウム ~健康長寿をめだした老化研究の最前線~
    • Place of Presentation
      明治安田生命ビルMY PLAZAホール(東京都・千代田区))
    • Related Report
      2016 Annual Research Report
  • [Presentation] A stress-responsive transcriptional factor NRF2 activates hematopoietic stem cells2015

    • Author(s)
      Shohei Murakami
    • Organizer
      57th ASH Annual Meeting and Exposition
    • Place of Presentation
      Orlando, FL, USA.
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A stress-responsive transcriptional factor NRF2 activates hematopoietic stem cells2015

    • Author(s)
      Shohei Murakami
    • Organizer
      44th Annual Scientific Meeting of the International Society for Experimental Hematology
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 造血幹細胞におけるKEAP1-NRF2制御系の機能解析2015

    • Author(s)
      村上昌平
    • Organizer
      日本生化学会東北支部 第81回例会・シンポジウム
    • Place of Presentation
      東北大学 さくらホール(宮城県・仙台市)
    • Year and Date
      2015-05-09
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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