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Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions

Author

Listed:
  • Kiyoka Saito

    (Kumamoto University
    Lund University)

  • Mark Garde

    (Lund University
    Technical University of Munich)

  • Terumasa Umemoto

    (Kumamoto University)

  • Natsumi Miharada

    (Kumamoto University)

  • Julia Sjöberg

    (Lund University)

  • Valgardur Sigurdsson

    (Lund University)

  • Haruki Shirozu

    (Kumamoto University)

  • Shunsuke Kamei

    (Kumamoto University)

  • Visnja Radulovic

    (Lund University)

  • Mitsuyoshi Suzuki

    (Lund University
    Juntendo University Faculty of Medicine)

  • Satoshi Nakano

    (Lund University
    Juntendo University Faculty of Medicine)

  • Stefan Lang

    (Lund University)

  • Jenny Hansson

    (Lund University)

  • Martin L. Olsson

    (Lund University)

  • Takashi Minami

    (Kumamoto University)

  • Gunnar Gouras

    (Lund University)

  • Johan Flygare

    (Lund University)

  • Kenichi Miharada

    (Kumamoto University
    Lund University)

Abstract

Hematopoietic stem cells (HSCs) react to various stress conditions. However, it is unclear whether and how HSCs respond to severe anemia. Here, we demonstrate that upon induction of acute anemia, HSCs rapidly proliferate and enhance their erythroid differentiation potential. In severe anemia, lipoprotein profiles largely change and the concentration of ApoE increases. In HSCs, transcription levels of lipid metabolism-related genes, such as very low-density lipoprotein receptor (Vldlr), are upregulated. Stimulation of HSCs with ApoE enhances their erythroid potential, whereas HSCs in Apoe knockout mice do not respond to anemia induction. VldlrhighHSCs show higher erythroid potential, which is enhanced after acute anemia induction. VldlrhighHSCs are epigenetically distinct because of their low chromatin accessibility, and more chromatin regions are closed upon acute anemia induction. Chromatin regions closed upon acute anemia induction are mainly binding sites of Erg. Inhibition of Erg enhanced the erythroid differentiation potential of HSCs. Our findings indicate that lipoprotein metabolism plays an important role in HSC regulation under severe anemic conditions.

Suggested Citation

  • Kiyoka Saito & Mark Garde & Terumasa Umemoto & Natsumi Miharada & Julia Sjöberg & Valgardur Sigurdsson & Haruki Shirozu & Shunsuke Kamei & Visnja Radulovic & Mitsuyoshi Suzuki & Satoshi Nakano & Stefa, 2024. "Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52509-w
    DOI: 10.1038/s41467-024-52509-w
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