Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection

Mistry, Jayna J., Hellmich, Charlotte, Moore, Jamie A., Jibril, Aisha, Macaulay, Iain, Moreno-Gonzalez, Mar, Di Palma, Federica, Beraza, Naiara, Bowles, Kristian M. and Rushworth, Stuart A. (2021) Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. Nature Communications, 12 (1). ISSN 2041-1723

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Abstract

Acute infection is known to induce rapid expansion of hematopoietic stem cells (HSCs), but the mechanisms supporting this expansion remain incomplete. Using mouse models, we show that inducible CD36 is required for free fatty acid uptake by HSCs during acute infection, allowing the metabolic transition from glycolysis towards β-oxidation. Mechanistically, high CD36 levels promote FFA uptake, which enables CPT1A to transport fatty acyl chains from the cytosol into the mitochondria. Without CD36-mediated FFA uptake, the HSCs are unable to enter the cell cycle, subsequently enhancing mortality in response to bacterial infection. These findings enhance our understanding of HSC metabolism in the bone marrow microenvironment, which supports the expansion of HSCs during pathogenic challenge.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 15 Dec 2021 17:30
Last Modified: 07 Jun 2022 00:24
URI: https://ueaeprints.uea.ac.uk/id/eprint/82702
DOI: 10.1038/s41467-021-27460-9

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