AlphaVbeta3 integrin bidirectionally regulates hematopoietic stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19560
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kumamoto 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
• 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.

Free Research Field

幹細胞生物学