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The determiniation of megakaryocyte lineage commitment of hematopoietic stem cells(Fostering Joint International Research)

Research Project

Project/Area Number 15KK0350
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

Nakamura-Ishizu Ayako  熊本大学, 国際先端医学研究機構, 客員准教授 (10548548)

Research Collaborator Suda Toshio  National University of Singapore, Cancer Science Institute, Principal investigator
MacArthur Ben D.  
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywords造血幹細胞 / 巨核球 / 単一細胞シークエンス解析 / 分化 / ミトコンドリア代謝 / ミトコンドリア / 単一細胞 / 細胞代謝 / 多様性 / トロンボポエチン / シングルセル解析
Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) are heterogeneous in differentiation potential. We analyzed BM HSCs for the identification of novel HSC subsets that are biased to Mk differentiation and the mechanism of how these HSCs emerge. We identified the cytokine, Thpo, rapidly skews HSC to Mk lineage differentiation. International collaboration with researchers in National University of Singapore enabled us to conduct single cell RNA sequence of HSCs from mice treated with Thpo. The data revealed that Thpo-treated HSCs were highly enriched with mitochondrial-related gene signature. The correlation of high mitochondrial content to Mk lineage differentiation was also confirmed in steady state HSCs with high mitochondria content. We also conducted ATAC sequencing in order to investigate change in chromatin accessibility in HSCs upon Thpo signaling. Collectively, our data indicate that mitochondrial metabolism and epigenetic changes maybe key mechanisms underlying Mk-lineage differentiation.

Academic Significance and Societal Importance of the Research Achievements

急激な出血や重度の炎症の際、生体は止血のために早急に血小板を産生する必要がある。このため、造血細胞のおおもととなる造血幹細胞は血小板を産生する巨核球細胞に偏って分化傾向を示す細胞群があることが示唆されている。当研究は、造血幹細胞の巨核球系への分化運命の決定のメカニズムを解析した。シンガポール国立大学の研究室と共同研究と行い、造血幹細胞の巨核球系の分化にサイトカインのひとつであるトロンボポエチンのシグナルが関与していることを解析した。また、同時にミトコンドリア代謝、エピジェネティック変化の解析を行った。

Report

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

    (6 results)

All 2018 2017

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Int'l Joint Research] Cancer Science Institute National University of Singapore(シンガポール)2018

    • Year and Date
      2018-06-04
    • Related Report
      2018 Annual Research Report
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / 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 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Thrombopoietin induces oxidative metabolism in hematopoietic stem cell differentiation2018

    • Author(s)
      Ayako Nakamura-Ishizu
    • Organizer
      MSC Cancer Program Symposium, NUS, Singapore
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Thrombopoietin mediates metabolic priming of hematopoietic stem cells for rapid megakaryocyte lineage differentiation2018

    • Author(s)
      Ayako Ishizu
    • Organizer
      Stem cell symposium
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Thrombopoietin-mediated exit from quiescence involves metabolic priming of hematopoietic stem cells for rapid megakaryocyte lineage differentiation2017

    • Author(s)
      Ayako Ishizu
    • Organizer
      ISEH
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2016-10-04   Modified: 2021-03-11  

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