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Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply

Author

Listed:
  • Chao Liu

    (University of California, San Diego)

  • Tianxu Han

    (University of California, San Diego)

  • David L. Stachura

    (University of California, San Diego)

  • Huawei Wang

    (University of California, San Diego)

  • Boris L. Vaisman

    (National Heart, Lung, and Blood Institute)

  • Jungsu Kim

    (University of California, San Diego)

  • Richard L. Klemke

    (University of California, San Diego)

  • Alan T. Remaley

    (National Heart, Lung, and Blood Institute)

  • Tariq M. Rana

    (University of California, San Diego)

  • David Traver

    (University of California, San Diego)

  • Yury I. Miller

    (University of California, San Diego)

Abstract

Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis.

Suggested Citation

  • Chao Liu & Tianxu Han & David L. Stachura & Huawei Wang & Boris L. Vaisman & Jungsu Kim & Richard L. Klemke & Alan T. Remaley & Tariq M. Rana & David Traver & Yury I. Miller, 2018. "Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03775-y
    DOI: 10.1038/s41467-018-03775-y
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    Cited by:

    1. Thi Tran & Jean-Remi Lavillegrand & Cedric Lereverend & Bruno Esposito & Lucille Cartier & Melanie Montabord & Jaouen Tran-Rajau & Marc Diedisheim & Nadège Gruel & Khadija Ouguerram & Lea Paolini & Ol, 2022. "Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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