Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions
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. Vldlr<sup>high</sup>HSCs show higher erythroid potential, which is enhanced after acute anemia induction. Vldlr<sup>high</sup>HSCs 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.
Authors
- Terumasa Umemoto (ORCID: https://orcid.org/0000-0003-0423-9003)
- Takashi Minami (ORCID: https://orcid.org/0000-0002-2345-1379)
- Stefan Lang (ORCID: https://orcid.org/0000-0002-0854-2328)
- Natsumi Miharada (ORCID: https://orcid.org/0000-0001-6989-5314)
- Martin L. Olsson (ORCID: https://orcid.org/0000-0003-1647-9610)
- Višnja Radulović
- Satoshi Nakano (ORCID: https://orcid.org/0000-0002-7010-9867)
- Jenny Hansson (ORCID: https://orcid.org/0000-0001-9174-8089)
- Gunnar K. Gouras (ORCID: https://orcid.org/0000-0002-5500-6325)
- Johan Flygare (ORCID: https://orcid.org/0000-0002-1962-5276)
- Mark van der Garde (ORCID: https://orcid.org/0000-0002-7227-0056)
- Valgarður Sigurðsson (ORCID: https://orcid.org/0000-0003-4146-7179)
- Julia Sjöberg (ORCID: https://orcid.org/0000-0002-0400-2025)
- Mitsuyoshi Suzuki (ORCID: https://orcid.org/0000-0002-9969-3454)
- Kenichi Miharada (ORCID: https://orcid.org/0000-0001-8073-4001)
- Haruki Shirozu
- Shunsuke Kamei
- Kiyoka Saito
Institutions
- Lund University (SE)
- Juntendo University (JP)
- Technical University of Munich (DE)
- Kumamoto University (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1038/s41467-024-52509-w
- Citations
- 7
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 2.29
Funders
- Stiftelsen för Strategisk Forskning
- Cancerfonden
- Lunds Universitet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Japan Society for the Promotion of Science