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Cell metabolism determines the megakaryocyte lineage fate of hematopoietic stem cells

Research Project

Project/Area Number 18K08364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionTokyo Women's Medical University (2019-2020)
Kumamoto University (2018)

Principal Investigator

Nakamura-Ishizu Ayako  東京女子医科大学, 医学部, 教授 (10548548)

Co-Investigator(Kenkyū-buntansha) 須田 年生  熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords造血幹細胞 / ミトコンドリア / 巨核球 / 静止期 / 分化 / トロンボポエチン / 静止性 / 代謝 / 細胞代謝
Outline of Final Research Achievements

The production of platelets in the bone marrow requires the differentiation of megakaryocytes (Mk) from hematopoietic stem cells (HSCs). This project aimed to delineate how the cytokine Thrombopoietin(Thpo) regulates Mk differentiation potential of HSCs. We identified that Thpo stimulates mitochondria metabolism in HSCs which skewed HSCs towards Mk lineage differentiation. Furthermore, we analyzed Thpo knock out mice and identified that Thpo signaling was required for maintaining HSCs in a quiescent state. Our research highlights the significance of Thpo signaling in regulating HSC differentiation and maintenance through modifications of mitochondria metabolism.

Academic Significance and Societal Importance of the Research Achievements

骨髄造血幹細胞の巨核球、血小板系統への分化バイアスメカニズムの詳細はわかっていない。本研究は、サイトカイン, Thrombopoietin(Thpo)によるミトコンドリアによるエネルギー代謝が造血幹細胞の巨核球分化に関与することを明確にした。生体外におけるHSCの増幅、分化は幹細胞を臨床治療に応用する際に重要であり、本研究はその手法の開発、改善のために役立つと思われる。また、造血幹細胞機能不全の起こる様々な血液疾患の病態解明、新規治療開発にも役立つと思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results)

  • [Journal Article] Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation2021

    • Author(s)
      Nakamura-Ishizu Ayako、Chin Desmond Wai Loon、Matsumura Takayoshi、Tan Darren Qiancheng、Mochizuki-Kashio Makiko、Jianwen Deng、Suda Toshio
    • Journal Title

      Blood

      Volume: 137 Issue: 19 Pages: 2609-2620

    • DOI

      10.1182/blood.2020005517

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hematopoietic Stem Cell Metabolism during Development and Aging2020

    • Author(s)
      Nakamura-Ishizu Ayako、Ito Keisuke、Suda Toshio
    • Journal Title

      Developmental Cell

      Volume: 54 Issue: 2 Pages: 239-255

    • DOI

      10.1016/j.devcel.2020.06.029

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multifaceted roles of thrombopoietin in hematopoietic stem cell regulation2019

    • Author(s)
      Nakamura‐Ishizu Ayako、Suda Toshio
    • Journal Title

      Annals of the New York Academy of Sciences

      Volume: ー Issue: 1 Pages: 1-8

    • DOI

      10.1111/nyas.14169

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thrombopoietin metabolically primes hematopoietic stem cells to megakaryocyte lineage differentiation2018

    • Author(s)
      Nakamura-Ishizu N, Matsumura T, Stumpf PS, Umemoto T, Takizawa H, Takihara Y, O’Neil A, Majeed ABBA, MacArthur BD., Suda T
    • Journal Title

      Cell Reports

      Volume: 25(7) Issue: 7 Pages: 1772-1785

    • DOI

      10.1016/j.celrep.2018.10.059

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Thrombopoietin regulates mitochondria homeostasis for HSC maintenance2020

    • Author(s)
      石津綾子
    • Organizer
      日本血液学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Thrombopoietin-mediated metabolic homeostasis for the maintenance of bone marrow hematopoietic stem cells2020

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      Hematology Meeting of Hematopoietic and Leukemic Stem Cells
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] “The multifaceted roles of thrombopoietin in hematopoietic stem cell maintenance”2019

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      Japan Association of Anatomists, regional meeting, Invited speaker,
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Quiescence induction in a Thpo-independent HSC subset2019

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      日本血液学会
    • Related Report
      2019 Research-status Report
  • [Presentation] A Thpo-independent HSC subset which can be induced to quiescence2019

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      Cancer Science Institute, CSI meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of Thpo-independent hematopoietic stem cells which are induced to quiescence2019

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      ISEH
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Thrombopoietin mediates metabolic priming of hematopoietic stem cells for rapid megakaryocyte lineage differentiation2018

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      Stem cell symposium, Kyushu University, Fukuoka, Japan
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Thrombopoietin induces oxidative metabolism in hematopoietic stem cell differentiation.2018

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      MSC Cancer Program Symposium, NUS, Singapore
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2025-01-30  

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