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Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions

Saito, Kiyoka LU ; van der Garde, Mark LU ; Umemoto, Terumasa ; Miharada, Natsumi LU ; Sjöberg, Julia LU ; Sigurdsson, Valgardur LU ; Shirozu, Haruki LU ; Kamei, Shunsuke ; Radulovic, Visnja LU and Suzuki, Mitsuyoshi LU , et al. (2024) In Nature Communications 15(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
8131
publisher
Nature Publishing Group
external identifiers
  • pmid:39284836
  • scopus:85204177856
ISSN
2041-1723
DOI
10.1038/s41467-024-52509-w
language
English
LU publication?
yes
id
31773397-036d-429b-80ce-be1eec6ad0f0
date added to LUP
2024-11-12 15:45:09
date last changed
2025-07-10 00:38:30
@article{31773397-036d-429b-80ce-be1eec6ad0f0,
  abstract     = {{<p>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.</p>}},
  author       = {{Saito, Kiyoka and van der Garde, Mark and Umemoto, Terumasa and Miharada, Natsumi and Sjöberg, Julia and Sigurdsson, Valgardur and Shirozu, Haruki and Kamei, Shunsuke and Radulovic, Visnja and Suzuki, Mitsuyoshi and Nakano, Satoshi and Lang, Stefan and Hansson, Jenny and Olsson, Martin L. and Minami, Takashi and Gouras, Gunnar and Flygare, Johan and Miharada, Kenichi}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-52509-w}},
  doi          = {{10.1038/s41467-024-52509-w}},
  volume       = {{15}},
  year         = {{2024}},
}