Mistry, Jayna J., Hellmich, Charlotte, Moore, Jamie A., Jibril, Aisha, Macaulay, Iain, Moreno-Gonzalez, Mar, Di Palma, Federica, Beraza, Naiara, Bowles, Kristian M. ORCID: https://orcid.org/0000-0003-1334-4526 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 |
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Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
Related URLs: | |
Depositing User: | LivePure Connector |
Date Deposited: | 15 Dec 2021 17:30 |
Last Modified: | 30 Jan 2024 02:51 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/82702 |
DOI: | 10.1038/s41467-021-27460-9 |
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