Effect of erythropoietin (EPO) and leukemia-inhibitory factor (LIF) on miRNA expression profiling in differentiating rat CG4-EPOR oligodendrocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE90973 | GEO | 2016/12/08
SECONDARY ACCESSION(S): PRJNA356543
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of the gene expression profile in differentiating rat CG4-EPOR oligodendrocytes treated with EPO, LIF or their combination for 1h or 20h Gene expression was measured undifferentiated CG4-EPOR cells and in differentiating cells at 1h and 20h in 5 conditions: control, EPO 10ng/ml, LIF 0.2ng/ml, LIF 10ng/ml, EPO 10ng/ml+LIF 10ng/ml); 3 or 4 replicates.
2016-07-22 | E-GEOD-84687 | biostudies-arrayexpress
Project description:Analysis of the gene expression profile in differentiating rat CG4-EPOR oligodendrocytes treated with EPO, LIF or their combination for 1h or 20h
2016-07-22 | GSE84687 | GEO
Project description:Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in the mammalian brain. In clinical settings, recombinant EPO had revealed a remarkable improvement of cognitive functions, but the underlying mechanisms have remained obscure. Animal studies demonstrated, however, that neuronal EPO effects are independent of an elevated hematocrit. Here, we show with a novel line of reporter mice that cognitive challenge leads to local/endogenous hypoxia in hippocampal pyramidal neurons where it induces enhanced expression of both EPO and EPO receptor (EPOR). High-dose EPO administration, which amplifies auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, improved performance on complex running wheels after EPO treatment is imitated by exposure to mild exogenous/inspiratory hypoxia. All these effects depend on neuronal expression of the Epor gene. Taken together, this suggests a novel cellular model of neuroplasticity in which neuronal networks, challenged by cognitive tasks, drift into transient hypoxia which becomes a trigger of neuronal EPO/EPOR expression. This regulatory circle causes long-lasting neuroplastic adaptation, and as fundamental cellular mechanism, may be relevant for strategies aiming at cognitive improvement.
2020-01-30 | GSE144444 | GEO
Project description:The regulatory system of erythropoiesis through erythropoietin (EPO) and its receptor (EPOR) is essential for vertebrates' life. In humans, EPO affects the erythroid progenitors and stimulates proliferation and differentiation. The EPO-EPOR axis is mainly mediated by the JAK2-STAT5 pathway. After terminal maturation, erythrocytes lost EPOR expression; however, erythrocytes of amphibian Xenopus tropicalis maintain EPOR expression even after their terminal maturation. Because erythrocytes of vertebrates except for adult mammals are nucleated, we hypothesized that EPO can alter its transcriptional state. To explore the effects of EPO on Xenopus mature erythrocytes, we performed RNA-Seq analysis on EPO-stimulated Xenopus peripheral blood cells. The EPO-stimulated group showed increased expression of direct target genes of STAT such as cish, socs3, and socs1 indicating a functional signal transduction system. Furthermore, we observed several EPO-responsive genes that were not reported in mammalian erythroid progenitors. These findings suggest the functional difference between enucleated erythrocytes in adult mammals and nucleated erythrocytes in fetal mammals and non-mammalian vertebrates.
2024-04-05 | GSE251901 | 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
Project description:Erythropoietin (EPO) has multiple functions beyond stimulating erythrocytosis, including modulation of T cell immunity. Effects EPO in transplantation and associated mechanisms remain incompletely understood. We analyzed outcomes and performed cellular and molecular mechanistic assessments in murine wild type (WT) and conditional EPO receptor (EPOR) knockout recipients of cardiac allografts. In translational studies, we tested EPO’s effects in a non-human primate system.
2023-03-01 | GSE199270 | GEO
Project description:Erythropoietin (EPO) is the primary regulator of erythropoiesis in the mammalian fetus and the adult through interaction with erythropoietin receptor (EPOR). Deficiency of EPO induces anemia that is a major cause of death in patients with chronic kidney disease. Thus, development of safe treatment for anemia is an urgent issue. In this study, we investigated the effect of γ-aminobutyric acid (GABA) on serum EPO level and erythropoiesis, and its mechanism was elucidated in rat. GABA significantly (P < 0.05) increased EPO level in serum and expression levels of EPO and EPOR in a dose dependent manner. GABA increased the expression levels of HIF-1 and HIF-2 in a dose dependent manner compared with the negative control; while GABA did not affect the expression of prolyl-hydroxylase domain protein-2α (PHD-2α) gene, an oxygen sensor. GABA supplementation alters energy production pathway resulted in hypoxic condition, which increases EPO level in rat through overexpression of HIF-1 and HIF-2. This study shows a new physiological role of GABA in EPO production and thus GABA could contribute to the prevention of anemia by using alone or in combination with other anemia treating drugs.
2020-03-04 | GSE146299 | GEO
Project description:In an attempt to validate the CG4 cell line as a model for oligodendrocytes, we determined the expression profiles in both cell types and the alterations during differentiation and found a striking overlap. Using CG4 cells as a model system for oligodendroglial cells, we generated several Nkx2.2 and Zfp488 overexpressing CG4 lines and compared their expression profile under differentiating conditions to regular CG4 cells to identify target genes of the two transcription factors in a genome-wide and unbiased approach. Several target genes were shared between Nkx2.2 and Zfp488, among them Gpr37.
2024-03-27 | GSE244592 | GEO
Project description:To gain further insight into the downstream effects of EPO signaling on HCC cells, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to illustrate EPO-induced the proliferation of HCC cells. 1×10e6 7721-EPOR cells were plated in 6 cm dishes and starved for 8 hours and then treated with either NS or EPO (10 IU/ml) for 16 hours. Total RNA was extracted and profiled using oligo microarrays. Differentially expressed genes were then identified through fold change as well as P value calculated with t-test. The threshold set for up- and down-regulated genes was a fold change>= 2.0 and a P value<= 0.05. Afterwards, GO analysis and KEGG analysis were applied to determine the roles of these differentially expressed mRNAs. EPO treated HCC cells up-regulated 14 genes expression and down-regulated 29 gene expression compared to control cells.
2017-05-01 | GSE81310 | GEO
Project description:Erythropoietin (EPO) and its receptor are highly expressed in the developing nervous system, and is exogenous EPO therapy is potentially neuroprotective, however the epigenetic and transcriptional changes downstream of EPO signaling in neural cells are not well understood. To delineate epigenetic changes associated with EPO signaling, we compared histone H3 lysine 4 dimethylation (H3K4me2) in EPO treated and control fetal neural progenitor cells, identifying 1,150 differentially bound regions. These regions were highly enriched near protein coding genes and had significant overlap with H4Acetylation, a mark of active regulatory elements. Motif analyses and co-occupancy studies revealed a complex regulatory network underlying the differentially bound regions, including previously identified mediators of EPO signaling (STAT5, STAT3), and novel factors such as REST, an epigenetic modifier central to neural differentiation and plasticity, and NRF1, a key regulator of antioxidant response and mitochondrial biogenesis. Global transcriptome analyses on neural tubes isolated from E9.0 EpoR-null and littermate control embryos validated our in vitro findings, further suggesting a role for REST and NRF1 downstream of EPO signaling. These data support a role for EPO in regulating the survival, proliferation, and differentiation of neural progenitor cells, and suggest a basis for its function in neural development and neuroprotection. The human sequencing data is not shared publicly due to privacy concerns, but is available from the investigators on request
2017-11-06 | GSE99372 | GEO