| First Author | Florez MA | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 12 | Pages | 108530 |
| PubMed ID | 33357430 | Mgi Jnum | J:302000 |
| Mgi Id | MGI:6489204 | Doi | 10.1016/j.celrep.2020.108530 |
| Citation | Florez MA, et al. (2020) Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2. Cell Rep 33(12):108530 |
| abstractText | During chronic infection, the inflammatory cytokine interferon gamma (IFNgamma) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNgamma hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we find that IFNgamma disrupts the normally close interaction between HSCs and CXCL12-abundant reticular (CAR) cells in the HSC niche. IFNgamma stimulation increases expression of the cell surface protein BST2, which we find is required for IFNgamma-dependent HSC relocalization and activation. IFNgamma stimulation of HSCs increases their E-selectin binding by BST2 and homing to the bone marrow, which depends on E-selectin binding. Upon chronic infection, HSCs from mice lacking BST2 are more quiescent and more resistant to depletion than HSCs from wild-type mice. Overall, this study defines a critical mechanism by which IFNgamma promotes niche relocalization and activation in response to inflammatory stimulation and identifies BST2 as a key regulator of HSC quiescence. VIDEO ABSTRACT. |
