| Literature DB >> 27738012 |
Kyoko Ito1,2,3, Raphaël Turcotte4, Jinhua Cui1,5, Samuel E Zimmerman1,6, Sandra Pinho1,5, Toshihide Mizoguchi1,5, Fumio Arai7, Judith M Runnels4, Clemens Alt4, Julie Teruya-Feldstein8, Jessica C Mar1,6,9, Rajat Singh2,10,11, Toshio Suda7,12, Charles P Lin4, Paul S Frenette1,2,3,5, Keisuke Ito13,2,3,5,11.
Abstract
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single-cell level a purified and minimally heterogeneous murine Tie2+ HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality control process in mitochondria, plays an essential role in self-renewing expansion of Tie2+ HSCs. Activation of the PPAR (peroxisome proliferator-activated receptor)-fatty acid oxidation pathway promotes expansion of Tie2+ HSCs through enhanced Parkin recruitment in mitochondria. These metabolic pathways are conserved in human TIE2+ HSCs. Our data thus identify mitophagy as a key mechanism of HSC expansion and suggest potential methods of cell-fate manipulation through metabolic pathways.Entities:
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Year: 2016 PMID： 27738012 PMCID： PMC5164878 DOI： 10.1126/science.aaf5530
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728