Effect of erythropoietin on the gene expression of Xenopus tropicalis peripheral blood cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Xenopus tropicalis
PROVIDER: GSE251901 | GEO | 2024/04/05
REPOSITORIES: GEO
Similar Datasets
Project description:Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells into more committed progenitors and finally into erythrocytes. Binding of erythropoietin to its receptor (EpoR) is strictly required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Jak2 tyrosine-kinase and Stat5a/b as a central pathway. Here, we demonstrate that phospholipase C gamma 1 (Plcγ1) is activated downstream of EpoR/Jak2 independently of Stat5. Plcγ1-deficient proerythroblasts and erythroid progenitors exhibited strong impairment in differentiation and colony-forming potential. In vivo, suppression of Plcγ1 in immunophenotypically defined hematopoietic stem cells (Lin-Sca1+KIT+CD48-CD150+) severely reduced erythroid development. To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation we assessed for changes on the level of transcription and DNA methylation after inactivation of Plcγ1. The single common downstream effector was H2AFY2, which encodes for the histone variant macroH2A2 (mH2A2). Suppression of macroH2A2 expression recapitulated the effects of Plcγ1 knockdown on erythroid maturation. Taken together, our findings identify Plcγ1 and its downstream target macroH2A2, as a ânon-canonicalâ signaling pathway essential for erythroid differentiation. MCIP-seq was used to interrogate methylation changes during Epo-induced differentiation of murine I/11 erythroblastic cell line upon knock-down of Plcy1 as compared to a mock control. Two different shRNA constructs that target Plcg1 were investigated at two different time points.
2015-12-31 | E-GEOD-60087 | biostudies-arrayexpress
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:Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells into more committed progenitors and finally into erythrocytes. Binding of erythropoietin to its receptor (EpoR) is strictly required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Jak2 tyrosine-kinase and Stat5a/b as a central pathway. Here, we demonstrate that phospholipase C gamma 1 (Plcγ1) is activated downstream of EpoR/Jak2 independently of Stat5. Plcγ1-deficient proerythroblasts and erythroid progenitors exhibited strong impairment in differentiation and colony-forming potential. In vivo, suppression of Plcγ1 in immunophenotypically defined hematopoietic stem cells (Lin-Sca1+KIT+CD48-CD150+) severely reduced erythroid development. To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation we assessed for changes on the level of transcription and DNA methylation after inactivation of Plcγ1. The single common downstream effector was H2AFY2, which encodes for the histone variant macroH2A2 (mH2A2). Suppression of macroH2A2 expression recapitulated the effects of Plcγ1 knockdown on erythroid maturation. Taken together, our findings identify Plcγ1 and its downstream target macroH2A2, as a “non-canonical” signaling pathway essential for erythroid differentiation.
2015-12-31 | GSE60087 | GEO
Project description:Chicken erythrocytes are nucleated cells often referred to as transcriptionally inactive, although the epigenetic changes and chromatin remodeling that mediate transcriptional repression and the extent of gene silencing during avian terminal erythroid differentiation are not fully understood. Here we characterized the changes in gene expression, chromatin accessibility, genome organization, and chromatin nuclear disposition during the terminal stages of erythropoiesis in chicken and found a complex chromatin reorganization at different genomic scales. We identified a robust decrease in transcription in erythrocytes. Nevertheless, a set of genes maintains their expression in erythrocytes, including genes involved in RNA pol II promoter-proximal pausing. Erythrocytes exhibit an inverted nuclear architecture and reposition euchromatin towards the nuclear periphery together with the paused RNA polymerase. In erythrocytes, chromatin domains are partially lost genome-wide except at mini domains retained around paused promoters. Our results suggest that promoter-proximal pausing of the RNA pol II participates in the transcriptional regulation of the erythroid genome and highlight the role of RNA polymerase in the maintenance of local chromatin organization.
2023-06-08 | GSE228694 | GEO
Project description:Chicken erythrocytes are nucleated cells often referred to as transcriptionally inactive, although the epigenetic changes and chromatin remodeling that mediate transcriptional repression and the extent of gene silencing during avian terminal erythroid differentiation are not fully understood. Here we characterized the changes in gene expression, chromatin accessibility, genome organization, and chromatin nuclear disposition during the terminal stages of erythropoiesis in chicken and found a complex chromatin reorganization at different genomic scales. We identified a robust decrease in transcription in erythrocytes. Nevertheless, a set of genes maintains their expression in erythrocytes, including genes involved in RNA pol II promoter-proximal pausing. Erythrocytes exhibit an inverted nuclear architecture and reposition euchromatin towards the nuclear periphery together with the paused RNA polymerase. In erythrocytes, chromatin domains are partially lost genome-wide except at mini domains retained around paused promoters. Our results suggest that promoter-proximal pausing of the RNA pol II participates in the transcriptional regulation of the erythroid genome and highlight the role of RNA polymerase in the maintenance of local chromatin organization.
2023-06-08 | GSE206193 | GEO
Project description:Chicken erythrocytes are nucleated cells often referred to as transcriptionally inactive, although the epigenetic changes and chromatin remodeling that mediate transcriptional repression and the extent of gene silencing during avian terminal erythroid differentiation are not fully understood. Here we characterized the changes in gene expression, chromatin accessibility, genome organization, and chromatin nuclear disposition during the terminal stages of erythropoiesis in chicken and found a complex chromatin reorganization at different genomic scales. We identified a robust decrease in transcription in erythrocytes. Nevertheless, a set of genes maintains their expression in erythrocytes, including genes involved in RNA pol II promoter-proximal pausing. Erythrocytes exhibit an inverted nuclear architecture and reposition euchromatin towards the nuclear periphery together with the paused RNA polymerase. In erythrocytes, chromatin domains are partially lost genome-wide except at mini domains retained around paused promoters. Our results suggest that promoter-proximal pausing of the RNA pol II participates in the transcriptional regulation of the erythroid genome and highlight the role of RNA polymerase in the maintenance of local chromatin organization.
2023-06-08 | GSE206192 | GEO
Project description:Chicken erythrocytes are nucleated cells often referred to as transcriptionally inactive, although the epigenetic changes and chromatin remodeling that mediate transcriptional repression and the extent of gene silencing during avian terminal erythroid differentiation are not fully understood. Here we characterized the changes in gene expression, chromatin accessibility, genome organization, and chromatin nuclear disposition during the terminal stages of erythropoiesis in chicken and found a complex chromatin reorganization at different genomic scales. We identified a robust decrease in transcription in erythrocytes. Nevertheless, a set of genes maintains their expression in erythrocytes, including genes involved in RNA pol II promoter-proximal pausing. Erythrocytes exhibit an inverted nuclear architecture and reposition euchromatin towards the nuclear periphery together with the paused RNA polymerase. In erythrocytes, chromatin domains are partially lost genome-wide except at mini domains retained around paused promoters. Our results suggest that promoter-proximal pausing of the RNA pol II participates in the transcriptional regulation of the erythroid genome and highlight the role of RNA polymerase in the maintenance of local chromatin organization.
2023-06-08 | GSE206191 | 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.
2013-03-26 | GSE45479 | GEO
Project description:Erythrocytes represent the most abundant cell type of the bloodstream in all vertebrates. The principal feature that differenciates erythrocytes of non-mammals is that unlike mammals they mantain the nucleus in their terminal differentiation. While the main function associated to erythrocytes is the oxygen and carbon dioxide transport, some other functions, no less important, have been attributed to these cells. The focus of this study was to investigate the response of cultured chicken erythrocytes to bacterial lipopolysaccharide (LPS), bacterial peptidoglycan (PGN) and to the analog viral dsRNA Poly(I:C) using a comercial microarray platform from Agilent.
2011-11-22 | GSE33813 | GEO
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