TY - JOUR
T1 - Lipoprotein metabolism mediates hematopoietic stem cell responses under acute anemic conditions
AU - Saito, Kiyoka
AU - van der Garde, Mark
AU - Umemoto, Terumasa
AU - Miharada, Natsumi
AU - Sjöberg, Julia
AU - Sigurdsson, Valgardur
AU - Shirozu, Haruki
AU - Kamei, Shunsuke
AU - Radulovic, Visnja
AU - Suzuki, Mitsuyoshi
AU - Nakano, Satoshi
AU - Lang, Stefan
AU - Hansson, Jenny
AU - Olsson, Martin L.
AU - Minami, Takashi
AU - Gouras, Gunnar
AU - Flygare, Johan
AU - Miharada, Kenichi
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-52509-w
DO - 10.1038/s41467-024-52509-w
M3 - Article
C2 - 39284836
AN - SCOPUS:85204177856
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 8131
ER -