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Gene expression data of murine hematopoietic stem cells after anemic stress

ABSTRACT: Gene expression data of murine hematopoietic stem cells after anemic stress

PROVIDER: PRJNA875299 | ENA |

REPOSITORIES: ENA

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Gene expression data of murine hematopoietic stem cells after in vitro culture and anemic stress

Project description:Gene expression data of murine hematopoietic stem cells after in vitro culture and anemic stress

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Gene expression data of murine hematopoietic stem cells after anemic stress

Project description:Adult hematopoietic stem cells (HSCs) react to various stress conditions by rapidly proliferating and preferentially differentiating towards desired cell types. However, it is unclear whether and how HSCs respond to severe anemic conditions. Here we demonstrate that HSCs rapidly proliferate and enhance their erythroid potential upon induction of acute anemia. Under severe anemic conditions, the concentration of erythropoietin (EPO) does not increase in the bone marrow. Instead, lipoprotein profiles largely changed, and the concentration of apolipoprotein E (ApoE) increased. In HSCs, transcription levels of lipid metabolism-related genes such as very low-density lipoprotein receptor (Vldlr) were significantly up-regulated. Stimulation of HSCs with recombinant ApoE enhanced the erythroid potential, while HSCs of ApoE knockout mice did not respond to the hemolysis induction. We also found that VLDLRhighHSCs have higher erythroid differentiation potential, particularly after acute anemia induction. VLDLRhighHSCs were epigenetically distinct from VLDLRlowHSCs, as their chromatin accessibility was lower and more chromatin regions were closed upon acute anemia induction. Finally, we identified that the chromatin regions closed upon the acute anemia induction were mainly binding sites of a transcription factor Erg. Treatment of HSC with Erg inhibitor enhanced erythroid differentiation potential, as seen in the ApoE treatment. Our findings indicate that lipoprotein metabolism, particularly ApoE, plays a crucial role in HSC regulation under severe anemia conditions in a non-canonical fashion, unlike a conventional factor such as EPO.

2023-06-30 | GSE212392 | GEO

Expression data from murine hematopoietic stem cells

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Project description:Isolation of long-term reconstituting hematopoietic stem cell (HSC) has been possible by utilizing flow cytometry with a combination of multiple antibodies against cell surface markers. However those cell surface phenotypes do not represent functional HSC after in vitro culture. We compared gene expression profiling of phenotypic HSC (CD48-KSL cells) before and after in vitro culture, and discovered that cultured HSC express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSC can be divided into CD244- and CD244+ subpopulations, and only CD244- cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. Induction of CD244 may partially be triggered by induction of endoplasmic reticulum (ER) stress, as chemically induced ER stress signal increased CD244+ subpopulation while ER stress suppression using a molecular chaperone, TUDCA, decreased CD244+ population, which were correlated to the output of reconstitution assay. These data suggest CD244 positivity is a potent marker to exclude non-functional HSC after in vitro culture thereby useful to elucidate mechanism of functional decline of HSC during ex vivo treatment. It has been unknown whether HSC respond to acute anemic stress. We compared frequency and differentiation potential of HSC in steady-state vs acute anemic mice, and discovered that HSC rapidly expand upon the anemia induction and change their lineage balance to more erythrocytic.

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Expression data from human bone marrow hematopoietic stem and progenitor populations from elderly anemic patients

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