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AlphaVbeta3 integrin bidirectionally regulates hematopoietic stem cells

Research Project

Project/Area Number 15K19560
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

Umemoto Terumasa  熊本大学, 国際先端医学研究機構, 特任助教 (50620225)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords造血幹細胞 / サイトカインシグナル / インテグリン
Outline of Final Research Achievements

Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. Integrin β3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-γ (IFNγ) and β3 integrin signaling in HSC function by a novel definitive phenotyping of HSCs. Integrin αvβ3 suppressed HSC function in the presence of IFNγ, and impaired integrin β3 signaling mitigated IFNγ-dependent negative action on HSCs. During IFNγ stimulation, integrin β3 signaling enhanced STAT1-mediated gene expression via serine phosphorylation. These findings show that integrin β3 signaling intensifies the suppressive effect of IFNγ on HSCs, which indicates that cell adhesion via integrin αvβ3 within the BM niche acts as a context-dependent signal modulator to regulate the HSC function under both steady state and inflammatory conditions.

Report

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

    (5 results)

All 2016 2015

All Presentation (5 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Presentation] Integrin αvβ3 regulates long-term repopulating activity of hematopoietic stem cells through the double-edged influences.2016

    • Author(s)
      Terumasa Umemoto, Yu matsuzaki, Junichi Furusawa, Takayuki Yoshimoto, Masayuki Yamato, Toshio Suda
    • Organizer
      2nd Kumamoto IRCMS international symposium and 17th Kumamoto AIDA seminar
    • Place of Presentation
      Kumamoto
    • Year and Date
      2016-10-31
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 周辺環境に依存する Integrin αvβ3 による造血幹細胞活性の制御2016

    • Author(s)
      梅本 晃正
    • Organizer
      平成28年度新学術領域研究「学術研究支援基盤形成【先端モデル動物支援プラットフォーム】」若手支援技術講習会
    • Place of Presentation
      蓼科
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integrin αvβ3 regulates long-term repopulating activity of hematopoietic stem cells through the double-edged influences.2016

    • Author(s)
      Terumasa Umemoto, Yu matsuzaki, Junichi Furusawa, Takayuki Yoshimoto, Masayuki Yamato, Toshio Suda
    • Organizer
      第15回幹細胞シンポジウム
    • Place of Presentation
      淡路島
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integrin αvβ3 exerts double-edged effects on hematopoietic stem cells in response to STAT1 status2016

    • Author(s)
      Terumasa Umemoto, Yu matsuzaki, Junichi Furusawa, Takayuki Yoshimoto, Masayuki Yamato, Toshio Suda
    • Organizer
      Singapore-Japan joint symposium
    • Place of Presentation
      National University of Singapore
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Integrin αvβ3 による双方向的な造血幹細胞活性の制御2015

    • Author(s)
      梅本 晃正, 松崎 優, 大和 雅之, 古澤 純一, 善本 隆之, 須田 年生
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited

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

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