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

Author

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  • Jayna J. Mistry

    (Norwich Medical School, University of East Anglia, Norwich Research Park
    Earlham Institute, Norwich Research Park)

  • Charlotte Hellmich

    (Norwich Medical School, University of East Anglia, Norwich Research Park
    Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane)

  • Jamie A. Moore

    (Norwich Medical School, University of East Anglia, Norwich Research Park)

  • Aisha Jibril

    (Norwich Medical School, University of East Anglia, Norwich Research Park)

  • Iain Macaulay

    (Earlham Institute, Norwich Research Park)

  • Mar Moreno-Gonzalez

    (Gut Microbes and Health Institute Strategic Programme, Quadram Institute)

  • Federica Palma

    (Norwich Medical School, University of East Anglia, Norwich Research Park)

  • Naiara Beraza

    (Gut Microbes and Health Institute Strategic Programme, Quadram Institute)

  • Kristian M. Bowles

    (Norwich Medical School, University of East Anglia, Norwich Research Park
    Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane)

  • Stuart A. Rushworth

    (Norwich Medical School, University of East Anglia, Norwich Research Park)

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.

Suggested Citation

  • Jayna J. Mistry & Charlotte Hellmich & Jamie A. Moore & Aisha Jibril & Iain Macaulay & Mar Moreno-Gonzalez & Federica Palma & Naiara Beraza & Kristian M. Bowles & Stuart A. Rushworth, 2021. "Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27460-9
    DOI: 10.1038/s41467-021-27460-9
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    References listed on IDEAS

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    1. Filippo Veglia & Vladimir A. Tyurin & Maria Blasi & Alessandra Leo & Andrew V. Kossenkov & Laxminarasimha Donthireddy & Tsun Ki Jerrick To & Zach Schug & Subhasree Basu & Fang Wang & Emanuela Ricciott, 2019. "Fatty acid transport protein 2 reprograms neutrophils in cancer," Nature, Nature, vol. 569(7754), pages 73-78, May.
    2. Aurélie Hérault & Mikhail Binnewies & Stephanie Leong & Fernando J. Calero-Nieto & Si Yi Zhang & Yoon-A Kang & Xiaonan Wang & Eric M. Pietras & S. Haihua Chu & Keegan Barry-Holson & Scott Armstrong & , 2017. "Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis," Nature, Nature, vol. 544(7648), pages 53-58, April.
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