| First Author | Matatall KA | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 10 | Pages | 2584-2595 |
| PubMed ID | 27926863 | Mgi Jnum | J:241673 |
| Mgi Id | MGI:5903358 | Doi | 10.1016/j.celrep.2016.11.031 |
| Citation | Matatall KA, et al. (2016) Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation. Cell Rep 17(10):2584-2595 |
| abstractText | Chronic infections affect a third of the world's population and can cause bone marrow suppression, a severe condition that increases mortality from infection. To uncover the basis for infection-associated bone marrow suppression, we conducted repeated infection of WT mice with Mycobacterium avium. After 4-6 months, mice became pancytopenic. Their hematopoietic stem and progenitor cells (HSPCs) were severely depleted and displayed interferon gamma (IFN-gamma) signaling-dependent defects in self-renewal. There was no evidence of increased HSPC mobilization or apoptosis. However, consistent with known effects of IFN-gamma, transcriptome analysis pointed toward increased myeloid differentiation of HSPCs and revealed the transcription factor Batf2 as a potential mediator of IFN-gamma-induced HSPC differentiation. Gain- and loss-of-function studies uncovered a role for Batf2 in myeloid differentiation in both murine and human systems. We thus demonstrate that chronic infection can deplete HSPCs and identify BATF2 as a mediator of infection-induced HSPC terminal differentiation. |
