| First Author | Umemoto T | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 16 | Pages | 2390-2403 |
| PubMed ID | 28673932 | Mgi Jnum | J:244084 |
| Mgi Id | MGI:5912863 | Doi | 10.15252/embj.201796771 |
| Citation | Umemoto T, et al. (2017) Integrin alphavbeta3 enhances the suppressive effect of interferon-gamma on hematopoietic stem cells. EMBO J 36(16):2390-2403 |
| abstractText | Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. When HSC sense external stimuli, their adhesion status may be critical for determining HSC cell fate. The cell surface molecule, integrin alphavbeta3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin beta3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-gamma (IFNgamma) and beta3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs. Integrin alphavbeta3 suppressed HSC function in the presence of IFNgamma and impaired integrin beta3 signaling mitigated IFNgamma-dependent negative action on HSCs. During IFNgamma stimulation, integrin beta3 signaling enhanced STAT1-mediated gene expression via serine phosphorylation. These findings show that integrin beta3 signaling intensifies the suppressive effect of IFNgamma on HSCs, which indicates that cell adhesion via integrin alphavbeta3 within the BM niche acts as a context-dependent signal modulator to regulate the HSC function under both steady-state and inflammatory conditions. |
