FOXO3A directs a protective autophagy program in haematopoietic stem cells.

Authors: Warr MR; Binnewies M; Flach J; Reynaud D; Garg T; Malhotra R; Debnath J; Passegué E

Abstract: 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.

Journal: Nature
Date: Feb. 8, 2013
PMID: 23389440
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Categories: Hematopoietic Stem Cell, Autophagy
Citation:

Warr MR, Binnewies M, Flach J, Reynaud D, Garg T, Malhotra R, Debnath J, Passegué E (2013) FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature.



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