Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression data of murine hematopoietic stem cells after anemic stress

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE212392 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ATAC-seq of VLDLR+ vs VLDLR- HSCs after acute anemia induction

Project description: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 a crucial role in HSC regulation under severe anemic conditions.

2024-08-07 | GSE274144 | GEO

Receptor-mediated mitophagy regulates EPO production and protects against renal anemia

Project description:Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.

2021-05-07 | GSE158361 | GEO

The effect of PHZ-induced hemolytic anemia on HSCs [bisulfite-seq]

Project description:Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs revealed that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increased upon anemia and these HSCs exhibited enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promoted DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impaired erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augmented these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.

2023-12-04 | GSE182058 | GEO

The effect of PHZ-induced hemolytic anemia on HSCs [RNA-seq]

2023-12-04 | GSE178215 | GEO

Transcriptome of EpoR-/- CFU-E cells

Project description:During erythropoiesis, erythroid progenitor cells proliferate in response to erythropoietin (Epo) and progressively differentiate, which encompasses an increasing accumulation of iron-bound hemoglobin. The impact of Epo on these dynamic processes remained to be resolved. By combining the development of a time-collapsed super SILAC method with transcriptome analysis we examined Epo-induced alterations in the proteome of erythroid progenitor cells at the colony-forming unit erythroid stage (CFU E). We showed that the timing of a major increase in the transcription factors GATA1 and TAL1 precedes the cessation of cell cycle progression but coincides with a massive upregulation of enzymes of the heme biosynthetic pathway. A failure of this upregulation due to the absence of the Epo receptor resulted in massive iron accumulation in the fetal liver and dilation of the maternal vasculature in the placenta. Thus, Epo-induced dynamic proteome adaptations in CFU E cells not only prevent anemia but also severe iron-intoxication in embryos.

2022-09-22 | GSE108696 | GEO

ATAC-seq of VLDLR+ vs VLDLR- HSCs after acute anemia induction

Project description:ATAC-seq of VLDLR+ vs VLDLR- HSCs after acute anemia induction

| PRJNA1145272 | ENA

Functional Requirements for a Samd14-Capping Protein Complex in Stress Erythropoiesis

Project description:Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals – involving cooperation between SCF/c-Kit signaling and other signaling inputs – are required for the activation and function of erythroid precursors in anemia. Our prior work revealed that the Sterile Alpha Motif (SAM) Domain 14 (Samd14) gene is transcriptionally upregulated in a model of acute anemia. Samd14 expression increases the regenerative capacity of the erythroid system and promotes stress-dependent c-Kit signaling. However, the mechanism underlying Samd14’s role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and β heterodimers of the F-actin capping protein (CP) complex. Knockdown of the CP β subunit increased erythroid maturation in ex vivo cultures and decreased colony forming potential of stress erythroid precursors. In a genetic complementation assay for Samd14 activity, our results revealed that the Samd14-CP interaction is a determinant of erythroid precursor cell levels and function. Samd14-CP promotes SCF/c-kit signaling in CD71med spleen erythroid precursors.

2022-08-09 | PXD030467 | Pride

Erythropoietin promotes abdominal aortic aneurysm via angiogenesis and inflammatory infiltration in Apoe-/- and wild type mice

Project description:The present study was undertaken to test the hypothesis that EPO may promote the formation of abdominal aortic aneurysm (AAA) via angiogenesis and inflammatory response. We injected EPO in different doses to Apoe-/- and WT mice, used EPO mAb in Apoe-/- mice with AngII stimulation, injected a selective activator of the heterodimer receptors of EPO into Apoe-/- and WT mice, and created CRISPR-mediated EPOR knockout (Epor+/-Apoe-/-) mice. In addition, we measured serum EPO concentration in healthy controls and patients with AAA, and performed a series of in vitro and ex vivo experiments in ECs, SMCs, and macrophages. Our results showed that EPO dose-dependently promoted the formation of AAA, with a high occurrence rate in both Apoe-/- and WT mice, and there was a close relationship between serum concentration of EPO and the incidence of AAA in Apoe-/- and WT mice receiving AngII or EPO treatment. The major mechanism involved angiogenesis, inflammatory response, SMCs apoptosis and collagen degradation via EPO-EPOR-JAK2/STAT5 signaling pathway in vascular cells. Administration of EPO neutralizing antibody suppressed AngII-induced AAA formation, and the incidence of AAA was dramatically reduced in Epor+/-Apoe-/- versus Apoe-/- mice after AngII infusion. In addition, serum EPO concentration was substantially higher in patients with AAA than in healthy subjects and correlated with the size of AAA in patients. In conclusion, EPO promotes the formation of AAA in both Apoe-/- and WT mice likely via enhanced angiogenesis, inflammation, SMCs apoptosis and collagen degradation, and EPO/EPOR signaling is essential for AngII-induced and possibly human AAA.

2021-05-18 | GSE174556 | GEO

Expression profiles of bone marrow cells from model mice for erythropoietin-deficiency anemia (ISAM)

Project description:We established a novel mouse model for postnatal erythropoietin (Epo)-deficiency anaemia, designated ISAM (inherited super anemic mouse), using a transgenic complementation rescue technique. To identify Epo-regulated genes in vivo, we examined the mRNA expression profile in the bone marrow of ISAM 6 hours after recombinant human EPO (rHuEPO) administration.

2013-01-18 | GSE43585 | GEO

Hemeatopoietic stem cells but not multipotent progenitors drive erythropoiesis during chronic erythroid stress in EPO transgenic mice

Project description:The hematopoietic stem cell (HSC) compartment consists of a small pool of cells capable of replenishing all blood cells. Although it is established that the hematopoietic system is assembled as a hierarchical organization under steady-state conditions, emerging evidence suggests that distinct differentiation pathways may exist in response to acute stress. However, it remains unclear how different hematopoietic stem and progenitor cell subpopulations behave under sustained chronic stress. Here, by using adult transgenic mice over-expressing erythropoietin (EPO; Tg6) and a combination of in vivo, in vitro, and deep sequencing approaches, we found that HSCs respond differentially to chronic erythroid stress than their closely related multipotent progenitors (MPPs). Specifically, HSCs exhibit a vastly committed erythroid progenitor profile with enhanced cell division, while MPPs display erythroid and myeloid cell signatures and an accumulation of uncommitted cells. Thus, our results identify HSCs as master regulators of chronic stress erythropoiesis, potentially circumventing the hierarchical differentiation-detour.

2018-05-11 | GSE113053 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data