Header

UZH-Logo

Maintenance Infos

A single metabolite which modulates lipid metabolism alters hematopoietic stem/progenitor cell behavior and promotes lymphoid reconstitution


Giger, Sonja; Kovtonyuk, Larisa V; Utz, Sebastian G; Ramosaj, Mergim; Kovacs, Werner J; Schmid, Emanuel; Ioannidis, Vassilios; Greter, Melanie; Manz, Markus G; Lutolf, Matthias P; Jessberger, Sebastian; Knobloch, Marlen (2020). A single metabolite which modulates lipid metabolism alters hematopoietic stem/progenitor cell behavior and promotes lymphoid reconstitution. Stem Cell Reports, 15(3):566-576.

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.

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.

Statistics

Citations

Altmetrics

Downloads

2 downloads since deposited on 19 Oct 2020
2 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
04 Faculty of Medicine > Brain Research Institute
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Genetics
Life Sciences > Developmental Biology
Life Sciences > Cell Biology
Uncontrolled Keywords:fatty acid beta-oxidation; lipid metabolism; malonyl-CoA; metabolism; stem cells
Language:English
Date:8 September 2020
Deposited On:19 Oct 2020 16:41
Last Modified:01 Nov 2020 17:13
Publisher:Cell Press (Elsevier)
ISSN:2213-6711
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.stemcr.2020.07.021
PubMed ID:32857979

Download

Gold Open Access

Download PDF  'A single metabolite which modulates lipid metabolism alters hematopoietic stem/progenitor cell behavior and promotes lymphoid reconstitution'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)