A Single Metabolite which Modulates Lipid Metabolism Alters Hematopoietic Stem/Progenitor Cell Behavior and Promotes Lymphoid Reconstitution.

ABSTRACT: Fatty acid β-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

SUBMITTER: Giger S 

PROVIDER: S-EPMC7486304 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature