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

Jayna J. Mistry, Charlotte Hellmich, Jamie A. Moore, Aisha Jibril, Iain Macaulay, Mar Moreno-Gonzalez, Federica Di Palma, Naiara Beraza, Kristian M. Bowles, Stuart A. Rushworth

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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.
Original languageEnglish
Article number7130
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 8 Dec 2021

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