Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34880245.
- Also identified by DOI 10.1038/s41467-021-27460-9 and PMC identifier 8655073.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CD36 Antigens
- Fatty Acids
- Fatty Acids, Nonesterified
- Hematopoietic Stem Cells