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Cross-organ HSC trafficking during definitive hematopoiesis formation

Research Project

Project/Area Number 18J20690
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Developmental biology
Research InstitutionKumamoto University

Principal Investigator

瀬崎 真衣子  熊本大学, 医学教育部, 特別研究員(DC1)

Project Period (FY) 2018-04-25 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2020: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2019: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2018: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsdefinitive hematopoiesis / hematopoietic stem cells / stem cell heterogeneity / bone marrow / HSC trafficking / 3D whole-organ imaging / lineage tracing / mathematical modeling / hematopoietic switching / deep-learning analysis / EC remodeling
Outline of Annual Research Achievements

In this study, the cellular and molecular mechanism of hematopoietic stem cell (HSC) trafficking that occurs during definitive hematopoiesis formation was investigated in the fetal to neonatal mouse. Single-cell RNA-sequencing of P2 HSCs isolated from the bone marrow, liver and spleen revealed HSC heterogeneity. PCA analysis showed 3 distinct clusters of HSCs with unique HSC marker expression (varying levels of cKit, Sca-1, CD150 mean fluorescence intensity) and differentially expressed genes. Our functional analysis via in vitro CFU-F and in vivo 10-cell transplantation into lethally irradiated mice revealed striking differences among these 3 groups in their ability to generate colonies and donor chimerism. We are now investigating the biological significance of these HSC groups and their contribution to adult hematopoiesis via lineage tracing and knock-out or knock-down studies.

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results)

  • [Int'l Joint Research] University of Zurich(スイス)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Zurich(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Zurich(スイス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates2021

    • Author(s)
      Hashimoto Michihiro、Umemoto Terumasa、Nakamura-Ishizu Ayako、Matsumura Takayoshi、Yokomizo Tomomasa、Sezaki Maiko、Takizawa Hitoshi、Suda Toshio
    • Journal Title

      Blood Advances

      Volume: 5 Issue: 6 Pages: 1594-1604

    • DOI

      10.1182/bloodadvances.2020002410

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immuno-Modulation of Hematopoietic Stem and Progenitor Cells in Inflammation2020

    • Author(s)
      Sezaki Maiko、Hayashi Yoshikazu、Wang Yuxin、Johansson Alban、Umemoto Terumasa、Takizawa Hitoshi
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 585367-585367

    • DOI

      10.3389/fimmu.2020.585367

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of the Hematopoietic System: Role of Inflammatory Factors2019

    • Author(s)
      Hayashi Y#, Sezaki M#, Takizawa H*
    • Journal Title

      Wiley Interdiscip Rev Dev Biol

      Volume: 27 Issue: 4

    • DOI

      10.1002/wdev.341

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト化骨髄を形成するヒト間葉系幹・前駆細胞の解析2020

    • Author(s)
      瀬崎真衣子
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Spatiotemporal coordination of HSC transit and bone marrow remodeling during early hematopoiesis (口頭)2019

    • Author(s)
      瀬崎真衣子
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 成人造血形成における造血幹細胞の臓器間遊走2018

    • Author(s)
      瀬崎真衣子
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cross-organ HSC trafficking during definitive hematopoiesis formation2018

    • Author(s)
      瀬崎真衣子
    • Organizer
      The 2nd KU-KAIST Joint Symposium Workshop
    • Related Report
      2018 Annual Research Report

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Published: 2018-05-01   Modified: 2024-03-26  

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