A Single Metabolite which Modulates Lipid Metabolism Alters Hematopoietic Stem/Progenitor Cell Behavior and Promotes Lymphoid Reconstitution
Fatty acid beta-oxidation (FAO), the breakdown of lipids, is a metabolic pathway used by various stem cells. FAO levels are generally high during quiescence and downregulated with proliferation. The endogenous metabolite malonyl-CoA modulates lipid metabolism as a reversible FAO inhibitor and as a substrate for de novo lipogenesis. Here we assessed whether malonyl-CoA can be exploited to steer the behavior of hematopoietic stem/progenitor cells (HSPCs), quiescent stem cells of clinical relevance. Treatment of mouse HSPCs in vitro with malonyl-CoA increases HSPC numbers compared with nontreated controls and ameliorates blood reconstitution capacity when transplanted in vivo, mainly through enhanced lymphoid reconstitution. Similarly, human HSPC numbers also increase upon malonyl-CoA treatment in vitro. These data corroborate that lipid metabolism can be targeted to direct cell fate and stem cell proliferation. Physiological modulation of metabolic pathways, rather than genetic or pharmacological inhibition, provides unique perspectives for stem cell manipulations in health and disease.
article-S2213671120302988.pd.pdf
Publisher's version
openaccess
CC BY-NC-ND
1.31 MB
Adobe PDF
9293c46082e063a5da5950974d57e4e1
1-s2.0-S2213671120302988-main.pdf
openaccess
CC BY-NC-ND
1.31 MB
Adobe PDF
8c5fd3c9bc0e4d979f295db24addef48