| First Author | Warr MR | Year | 2013 |
| Journal | Nature | Volume | 494 |
| Issue | 7437 | Pages | 323-7 |
| PubMed ID | 23389440 | Mgi Jnum | J:194535 |
| Mgi Id | MGI:5474138 | Doi | 10.1038/nature11895 |
| Citation | Warr MR, et al. (2013) FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature 494(7437):323-7 |
| abstractText | Blood production is ensured by rare, self-renewing haematopoietic stem cells (HSCs). How HSCs accommodate the diverse cellular stresses associated with their life-long activity remains elusive. Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system. |
