Expression data from murine bone marrow erythroid progenitor cells at two early stages of development.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE42346 | GEO | 2012/11/17
SECONDARY ACCESSION(S): PRJNA181132
REPOSITORIES: GEO
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Project description:This study was designed to define erythropoietin (EPO) regulated genes in murine bone marrow erythroid progenitor cells at two stages of development, designated E1, and E2. E1 cells correspond to CFUe- like progenitors, while E2 cells are proerythroblasts. 14 samples were analyzed. 8 samples belong to the E1 stage and the remaning 6 samples correspond to the E2 stage. In the E1 stage, there are 4 controls and 4 treatment samples. The 4 samples in each group are biological replicates. Likewise in the E2 stage, there are 3 control and 3 treatment samples and the 3 samples in each group are biological replicates.
2012-11-17 | E-GEOD-42346 | biostudies-arrayexpress
Project description:Profiling of bone marrow-derived erythroid progenitor cells at E1 (CFU-e), E2 (proerythroblasts), and E3 (maturing erythroblast) stages of development under stress erythropoiesis conditions and in response to EPO challenge. MACS-isolated E1, E2, and E3 stage EPCs were cultured in SP34ex media for 6 hrs in the absence of hematopoietic growth factors and the presence of insulin (to enforce survival and anti-apoptotic effects) and then exposed to rhEPO for 90 minutes. Gene expression analysis was performed using Affymetrix Mouse Genome 430 2.0 arrays; microarray data were analyzed using Bioconductor for R.
2017-06-06 | E-MTAB-5373 | 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 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: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
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. Erythropoietin-induced gene expression in mouse bone marrow was measured at 6 hours after rHuEPO administration (3,000 U/kg). Three Epo-treated samples were analyzed, and two PBS-treated and one untreated samples were used as a control group.
2013-01-18 | E-GEOD-43585 | biostudies-arrayexpress
Project description:Background: It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival has also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods: Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results: In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes have specific expression just at certain stages of ontogeny (STATs, GRB2, CREBB). Beside continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression (NFKBIA, YWHAH). Conclusions: This broad overview of gene expression in erythropoiesis revealed transcription factors with a prevalence at certain stages of ontogenesis. Finally, our results show that EPO-mediated proliferation and survival of erythroid progenitors occurs mainly through modulation of JAK-STAT pathway associated STATs, GRB2 and PIK3 genes, as well as AKT pathway- coupled NFKBIA and YWHAH genes.
2012-06-01 | GSE37869 | GEO
Project description:We have 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 responsible signals for myofibroblastic transformation of Renal Erythropoietin-producing cells (REPs), we examined the mRNA expression profile of whole ISAM kidneys that underwent reversible UUO model.
2013-03-20 | GSE45304 | GEO
Project description:Background: It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival has also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods: Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results: In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes have specific expression just at certain stages of ontogeny (STATs, GRB2, CREBB). Beside continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression (NFKBIA, YWHAH). Conclusions: This broad overview of gene expression in erythropoiesis revealed transcription factors with a prevalence at certain stages of ontogenesis. Finally, our results show that EPO-mediated proliferation and survival of erythroid progenitors occurs mainly through modulation of JAK-STAT pathway associated STATs, GRB2 and PIK3 genes, as well as AKT pathway- coupled NFKBIA and YWHAH genes. Adult peripheral blood mononuclear cells were isolated from buffy coats of 3 healthy donors using Lymphocyte Separation Medium (BioWhittaker, Walkersville, MD). We washed mononuclear cells twice with Dulbecco's phosphate-buffered saline (PBS, Invitrogen Corporation, Carlsbad, CA), and CD34+ cells were purified by positive immunomagnetic selection using the MACS cell isolation system (Miltenyi Biotec, Auburn, CA). Fresh bone marrow CD34+ cells were collected (AllCells LLC, Berkeley, CA). Cord blood CD34+ cells (AllCells LLC) and fetal liver CD34+ cells (Cambrex Bio Science, Inc., Walkersville, MD) were collected and frozen. For analysis, CD34+ cells were resuspended in medium, which contained 30% FBS, 2 mmol/L glutamine, 100 U/ml penicillin, 100 µg/ml streptomycin, 1% deionized BSA, 10 mmol/L beta-mercaptoethanol, 1 mmol/L dexamethasone, 33 µg/ml holo-transferrin, 10 ng/ml SCF, 1 ng/ml IL-3 and 1 ng/ml GM-CSF (Sigma, St. Louis, MO), and 1 U/ml human recombinant EPO (Amgen Inc, Thousand Oaks, CA) Erythroid progenitor cells differentiated from hematopoietic CD34+ progenitor cells of fetal liver, cord blood, bone marrow and peripheral blood origin Biological replicates: 2 fetal liver, 3 cord blood, 3 bone marrow, 3 peripheral blood origin
2012-05-31 | E-GEOD-37869 | 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:Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. However, a prolonged sojourn at high altitude results in an increase in EPO levels followed by a decrease, although erythropoiesis remains elevated at a stable level. The role of hypoxia and related EPO adjustments are not fully understood and contributed to the formulation of the theory of neocytolysis. In this study, we aimed to exclusively evaluate the role of oxygen on erythropoiesis comparing in vitro erythroid differentiation performed at atmospheric oxygen, with a lower oxygen concentration (3% O2) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in a different erythroid development, suggesting no retention of high altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at 3% oxygen, displaying a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation to the concept of neocytolysis.
2022-04-06 | PXD031776 | Pride