Glucocorticoids regulate murine megakaryocyte transcriptome
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198800 | GEO | 2023/06/26
REPOSITORIES: GEO
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Project description:Glucocorticoids regulate murine megakaryocyte transcriptome
| PRJNA817170 | ENA
Project description:Analysis of mRNA gene expression changes mediated by synthetic GR-agonist dexamethasone in mouse cortical primary astrocyte cultures Total RNA obtained from astrocyte cultures subjected to 0.25, 1, 2, 4, 6, 12, 18, or 24 hours of ~100nM dexamethasone exposure compared to vehicle control astrocyte cultures
2014-06-25 | E-GEOD-39272 | biostudies-arrayexpress
Project description:A mutation in the dimerization domain of the mouse glucocorticoid receptor (GR), dim1, has recently been shown to bind DNA and regulate gene expression. To expand these studies we created a stable osteosarcoma (U-2 OS) cell line expressing four mutations in the dimerization domain of the human GR, dim4 (N454D, A458T, R460D, D462C), and used whole human genome microarray analysis to compare differences in gene regulation between vehicle treated (CON) and those treated with the glucocorticoid receptor agonist dexamethasone (DEX) at 100nM concentration for 6 hours. Gene expression in U-2 OS hGRdim4 cells was measured after a 6 hour treatment with 100nM dexamethasone or vehicle (control) and the dexamethsone (dex) treated cells were compared to vehicle treated cells. The experiment was performed in triplicate.
2011-12-22 | E-GEOD-26857 | biostudies-arrayexpress
Project description:This study aims to identify all genes expressed in primary mouse megakaryocytes Keywords: Megakaryocyte, SAGE, transcriptome analysis Mouse megakaryocytes were grown in vitro from bone marrow progenitors. Mature, polyploid (approximately 95% 64n and 128n) differentiated megakaryocytes were used to generate RNA for SAGE library construction.
2007-02-02 | E-GEOD-6940 | biostudies-arrayexpress
Project description:The transcription factor Growth Factor Independence 1B (GFI1B) recruits Lysine Specific Demethylase 1A (LSD1/KDM1A) to stimulate gene programs relevant for megakaryocyte and platelet biology. Inherited pathogenic GFI1B variants result in thrombocytopenia and bleeding propensities with varying intensity. Whether these affect similar gene programs is unknow. Here we studied transcriptomic effects of four patient-derived GFI1B variants (GFI1BT174N,H181Y,R184P,Q287*) in MEG01 megakaryoblasts. Compared to normal GFI1B, each variant affected different gene programs with GFI1BQ287* uniquely failing to repress myeloid traits. In line with this, single cell RNA-sequencing of induced pluripotent stem cell (iPSC)-derived megakaryocytes revealed a 4.5-fold decrease in the megakaryocyte/myeloid cell ratio in GFI1BQ287* versus normal conditions. Inhibiting the GFI1B-LSD1 interaction with small molecule GSK-LSD1 resulted in activation of myeloid genes in normal iPSC-derived megakaryocytes similar as observed for GFI1BQ287* iPSC-derived megakaryocytes. Thus, GFI1B and LSD1 facilitate gene programs relevant for megakaryopoiesis while simultaneously repressing programs that induce myeloid differentiation.
2024-03-28 | PXD050401 | Pride
Project description:Glucocorticoids are an essential component of the treatment of lymphoid malignancies and resistance to glucocorticoid therapy constitutes a prominent clinical problem in relapsed and refractory lymphoblastic leukemias. Constitutively active NOTCH signaling is involved in the pathogenesis of over 50% of T-cell lymphoblastic leukemia (T-ALL) which harbor activating mutations in the NOTCH1 gene. Aberrant NOTCH1 signaling has been shown to protect normal thymocytes from glucocorticoid induced cell death. Here we analyzed the interaction of glucocorticoid therapy with inhibition of NOTCH signaling in the treatment of T-ALL. Gamma-secretase inhibitors (GSI), which block the activation of NOTCH receptors, amplified the transcriptional changes induced by glucocorticoid treatment, including glucocorticoid receptor autoinduction and restored sensitivity to dexamethasone in glucocorticoid-resistant T-ALL cells. Apoptosis induction upon inhibition of NOTCH signaling and activation of the glucocorticoid receptor was dependent on transcriptional upregulation of BIM and subsequent activation of the mitochondrial/intrinsic cell death pathway. Finally, we used a mouse xenograft model of T-ALL to demonstrate that combined treatment with dexamethasone and a GSI results in improved antileukemic effects in vivo. These studies provide insight in the mechanisms of glucocorticoid resistance and serve as rationale for the use of glucocorticoid and GSIs in combination in the treatment of T-ALL. Experiment Overall Design: Duplicate samples (biologic replicas) from CUTLL1 cells were treated for 24 hours with vehicle only (DMSO), dexamethasone (1microM), a gamma-secretase inhibitor (CompE 100nM) and a combination of dexamethasome plus gamma secretase inhibitor at the same concentrations indicated before. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (CompE) or the combination of both treatments.
2009-01-13 | E-GEOD-7067 | biostudies-arrayexpress
Project description:To clarify the machinery how lenalidomide inhibit proplatelet formation of megakaryocytes, we performed transcriptome analysis of megakaryocytes derived from human hematopoietic stem/progenitor cells in the liquid culture system with or without lenalidomide. Differentially expressed genes were comprehensively evaluated by gene set enrichment analysis. Untreated megakaryocytes showed the estradiol-responded gene expression signatures, whereas the lenalidomide-treated megakaryocytes did not. Furthermore, we performed a rescue strategy with exogenous estradiol, confirming that lenalidomide-induced inhibition of proplatelet formation should be due to the deficiency of endogenous estradiol action in megakaryocytes.
2018-06-30 | GSE111994 | GEO
Project description:We examined Glucocorticoid receptor binding sites in isolated neonatal cardiomyocytes treated with Dexamethasone (100nM) for 1hr or Ethanol using GR-ChIP-Seq. In addition to determine the change in the resulting transcriptional status of genes we performed RNAseq in cardiomyocytes treated with Dexamethasone (100nM) or Ethanol for 1hr or 24hrs.
2019-08-20 | GSE114766 | GEO
Project description:This study aims to identify all genes expressed in primary mouse megakaryocytes Keywords: Megakaryocyte, SAGE, transcriptome analysis
2007-02-03 | GSE6940 | GEO
Project description:Objective: Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. However, their use is associated with neurodevelopmental delay and cerebral palsy. We hypothesized that postnatal dexamethasone or betamethasone in high-dose, but not low-dose, would induce hypomyelination, astrogliosis, and motor impairment in premature rabbit pups. Additionally, these effects would be mediated by glucocorticoid receptors (GRs). Methods: Preterm rabbit pups, delivered by C-section at E29 (term=32d), were treated with a high dose of dexamethasone or vehicle. Myelin basic protein (MBP), glial fibrillary basic protein (GFAP), oligodendrocyte proliferation and maturation, and alteration of transcriptomic profile were evaluated in these pups. Neurobehavioral assessments were performed at 14d. Results: High-dose dexamethasone treatment reduced MBP expression and induced motor-impairment compared with controls. High-dose dexamethasone induced astrogliosis and altered genes associated with myelination, cell-cycle, GR, and MAP-Kinase signaling. Interpretation: High-dose postnatal dexamethasone arrested maturation of oligodendrocytes, and induced hypomyelination, gliosis and motor deficits. GC treatment reduced myelination by genomic GR-dependent mechanisms, and caused astrogliosis by non-genomic mechanisms.
2013-02-27 | GSE44610 | GEO