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

Details

Serval ID
serval:BIB_4276557C90C9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Single Metabolite which Modulates Lipid Metabolism Alters Hematopoietic Stem/Progenitor Cell Behavior and Promotes Lymphoid Reconstitution.
Journal
Stem Cell Reports
Author(s)
Giger S., Kovtonyuk L.V., Utz S.G., Ramosaj M., Kovacs W.J., Schmid E., Ioannidis V., Greter M., Manz M.G., Lutolf M.P., Jessberger S., Knobloch M.
ISSN
2213-6711 (Electronic)
ISSN-L
2213-6711
Publication state
Published
Issued date
08/09/2020
Peer-reviewed
Oui
Volume
3
Number
15
Pages
566-576
Language
english
Notes
Publication types: Journal Article
Publication Status: published
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 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.
Keywords
fatty acid beta-oxidation, lipid metabolism, malonyl-CoA, metabolism, stem cells
Pubmed
Open Access
Yes
Create date
09/09/2020 9:45
Last modification date
19/09/2020 5:26
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