The effect of PHZ-induced hemolytic anemia on HSCs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA754382 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14816473.fastq.gz | Fastqsanger.gz | |||
| SRR14816474.fastq.gz | Fastqsanger.gz | |||
| SRR14816475.fastq.gz | Fastqsanger.gz | |||
| SRR14816476.fastq.gz | Fastqsanger.gz | |||
| SRR14816477.fastq.gz | Fastqsanger.gz |
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Project description:The effect of PHZ-induced hemolytic anemia on HSCs [RNA-seq]
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Project description:The effect of PHZ-induced hemolytic anemia on HSCs [bisulfite-seq]
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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 | GSE178215 | GEO
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-12-04 | GSE182059 | GEO
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
Project description:Study was performed to improve understanding of erythropoiesis (EP) induced by acute anemia in Atlantic salmon. Fish was injected with a low dose of hemolytic compound phenylhydrazine (PHZ). Treatment resulted in moderate but significant reduction of hematocrit (Hct) and increased transcription of cardiac erythropoietin (epo) at 2 days post challenge (dpc), and epo receptor (epor) in spleen from 2 to 4 dpc. Oligonucleotide microarrays were used to characterize the events of EP in the spleen. These results were compared to gene expression profiles of untreated mature red blood cells (RBC) in order to search for erythroid-specific genes. Splenic responses suggested a prevalence of protective mechanisms at the first stage, characterized by induced xenobiotic metabolism and responses to oxidative and protein stress. Erythroid-specific regulation was evident at 2 dpc and enhanced by 4 dpc, and gene expression profiles witnessed a rapid establishment of RBC phenotype although Hct levels remained low. A large group of genes showed a strong correlation to globins by expression profiles. In addition to epor this included genes of heme and iron metabolism, scavengers of free radicals and chaperones, channels and transporters, markers of erythrocytes, regulators of proliferation and cell cycle arrest and many genes with unidentified roles in RBC differentiation. Induced EP in spleen was characterized by specific features, such as upregulation of virus-responsive genes and sustained high expression of proapoptotic genes including caspases. Transcriptome changes suggested an association between EP and suppression of several developmental programs including adaptive immune responses. In conclusion, acute hemolysis and resulting anemia rapidly induced EP in the spleen of Atlantic salmon, which showed both common characteristics for all vertebrates as well as fish-specific properties. Atlantic salmon was injected with a single dose of PHZ (6 mg/kg body mass) or saline. Spleen samples for microarray analyses were collected after 2 and 4 days. Additonally, red blood cells (RBC) were compared with spleen
2013-03-26 | E-GEOD-45479 | biostudies-arrayexpress
Project description:We investigated the RBCs of a hemolytic anemia patient using quantitative proteomics. We used stable isotope dimethyl labeling to accurately quantify the RBC proteins. As controls, 1) samples of four healthy subjects were taken to account for normal variation in healthy individuals, and 2) samples of two non-spherocytic hemolytic anemia patients were taken to account for differences in protein levels due to elevated reticulocyte content. We used a combination of strong cation exchange (SCX) chromatography with nanoLC-MS/MS, enabling quantification of RBC proteins.
2016-09-27 | PXD001837 | Pride