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Understanding the impact of gut inflammation-induced stress on hematopoiesis

Research Project

Project/Area Number 18K16091
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKumamoto University

Principal Investigator

Hayashi Yoshikazu  熊本大学, 国際先端医学研究機構, 特任助教 (00801078)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords造血幹細胞 / 多能性前駆細胞 / 腸管炎症 / 腸内細菌 / 自然免疫 / TLRシグナル / 細胞分化 / 細胞遊走 / Bacteroides / Gr-1細胞 / 造血幹・前駆細胞 / 造血応答 / 炎症性老化
Outline of Final Research Achievements

The previous report has shown that gram negative bacterial infection directly activates innate immune signaling in the dormant hematopoietic stem cells (HSCs) to induce proliferation and proliferative stress, eventually leading to functional impairment. Given as many commensal bacteria as human cells in our body, we hypothesized that microbial infiltration upon colitis might affect early hematopoiesis in bone marrow (BM). Then we tested this by employing dextran sulfate sodium (DSS)-induced colitis mouse model. Acute colitis expanded the hematopoietic stem and progenitor cells (HSPCs) in BM and the mesenteric lymph node, which is an inflammatory site. Acute colitis did not expand HSPCs of TRIF/Myd88-deficient mice in BM or MLN, indicating that HSPC expansion upon colitis is regulated via TLR signaling.

Academic Significance and Societal Importance of the Research Achievements

“炎症と造血”は造血分野において近年ホットな研究領域であり、老化に伴い増加する炎症疾患との関連性だけでなく生体防御や組織損傷・修復における機能の観点からも注目を集めている分野である。本研究では炎症反応の起こる場である血液の幹細胞(造血幹細胞)をモデルとして、これまで明らかにされてこなかった腸管炎症下における腸内細菌依存的な造血応答制御を分子レベルで明らかにした。腸内細菌関連分子を新たな造血制御因子として捉えており、造血における新たなバイオロジーを提示したという点において、基礎医学への貢献は大きく学術的意義ならびに社会的意義の高い研究である。

Report

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

    (14 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Int'l Joint Research] KAIST(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] KAIST(韓国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity.2020

    • Author(s)
      Suzuki D, Flahou C, Yoshikawa N, Stirblyte I, Hayashi Y, Sawaguchi A, Akasaka M, Nakamura S, Higashi N, Xu H, Matsumoto T, Fujio K, Manz MG, Hotta A, Takizawa H, Eto K, Sugimoto N.
    • Journal Title

      Stem Cell Reports.

      Volume: 14 Issue: 1 Pages: 49-59

    • DOI

      10.1016/j.stemcr.2019.11.011

    • NAID

      120006777032

    • Related Report
      2019 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
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammation and early hematopoiesis2018

    • Author(s)
      滝澤 仁、林 慶和
    • Journal Title

      Rinsho Ketsueki

      Volume: 59 Issue: 10 Pages: 1955-1961

    • DOI

      10.11406/rinketsu.59.1955

    • NAID

      130007496839

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Research-status Report
  • [Presentation] Microbial signal instructs early hematopoiesis upon intestinal tissue damage2019

    • Author(s)
      Hayashi Y, Sezaki M, Sheoran S, Morishima T, Nakato G, Fukuda S, Takizawa H.
    • Organizer
      48th Annual Scientific Meeting of International Society of Experimental Hematology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Early hematopoiesis translates microbial signals to intestinal tissue repair2019

    • Author(s)
      Hayashi Y, Takizawa H, Sezaki M, Sheoran S, Morishima T, Nakato G, Biswas S, Fukuda S.
    • Organizer
      24th Congress of the European Hematology Association
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Acute gut inflammation orchestrates early hematopoiesis via innate immune signaling2019

    • Author(s)
      Hayashi Y, Sheoran S, Morishima T, Nakato G, Fukuda S, Takizawa H.
    • Organizer
      17th Stem Cell Research Symposium
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gut microbiota orchestrates early hematopoiesis upon gut inflammation2019

    • Author(s)
      Hayashi Y, Fukuda S, Takizawa H
    • Organizer
      The 48th Japanese Society for Immunology 2019/
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microbial signal regulates crosstalk between bone marrow and other organs in early hematopoiesis2019

    • Author(s)
      Hayashi Y
    • Organizer
      The 3rd KU - KAIST Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 自然免疫シグナルは腸管炎症下における造血応答を制御する2019

    • Author(s)
      Hayashi Y, Sezaki M, Nakato G, Sheoran S, Morishima T, Fukuda S, Takizawa H.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] タイトル:成人造血形成における造血幹細胞移行と骨髄リモデリングの時空間的供応2019

    • Author(s)
      Sezaki M, Sham KYC, Hayashi Y, Haeno H, Yokomizo T, Nombela-Arrieta C, Laurenti E, Takizawa H
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Acute gut inflammation shifts early hematopoiesis toward myelopoiesis2018

    • Author(s)
      Hayashi Y, Hitoshi T
    • Organizer
      16th Stem Cell Research Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸管炎症は造血幹前駆細胞に対して分化バイアスを引き起こす2018

    • Author(s)
      林慶和、瀬崎麻衣子、滝澤仁
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-12-27  

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