Glucocorticoids regulate murine megakaryocyte transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA817170 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Total RNA from in vitro-differentiated murine megakaryocytes incubated for 6hr with 100nM dexamethasone or its vehicle was analyzed using a genome-wide expression microarray using Affymetrix Mouse Transcriptome Array 1.0 arrays.
2023-06-26 | GSE198800 | GEO
Project description:BackgroundGlucocorticoids are widely known for their immunomodulatory action. Their synthetic analogs are used to treat several autoimmune diseases, including immune thrombocytopenia. However, their efficacy and mechanisms of action in immune thrombocytopenia are not fully understood.ObjectivesTo investigate the mechanism of glucocorticoid actions on platelet production.MethodsThe actions of glucocorticoids on platelet production were studied combining in vivo, ex vivo and in vitro approaches.ResultsDexamethasone reduced bleeding in mice and rapidly increased circulating young platelet counts. In vitro glucocorticoid treatment stimulated proplatelet formation by megakaryocytes and platelet-like particle release. This effect was blocked by glucocorticoid receptor antagonist RU486, indicating a glucocorticoid receptor-dependent mechanism. Genome-wide analysis revealed that dexamethasone regulates the expression of >1000 genes related to numerous cellular functions, including predominant cytoplasm and cytoskeleton reorganization. Dexamethasone and other glucocorticoids induced the expression of Gda (the gene encoding guanine deaminase), which has been reported to have a role in dendrite development. Inhibition of guanine deaminase enzymatic activity blocked dexamethasone stimulation of proplatelet formation, implicating a critical role for this enzyme in glucocorticoid-mediated platelet production.ConclusionOur findings identify glucocorticoids as new regulators of thrombopoiesis.
| S-EPMC10592358 | biostudies-literature
Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from C57/BL6 murine fetal liver and bone marrow
2013-03-29 | E-GEOD-45618 | biostudies-arrayexpress
Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from GATA1s fetal liver and bone marrow
2013-03-29 | E-GEOD-45619 | biostudies-arrayexpress
Project description:MicroRNAs are small non-coding RNAs that regulate cellular development by interfering with mRNA stability and translation. We defined the kinetics of global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were upregulated and 81 were downregulated. Many of these changes are consistent with miRNA profiling studies of human megakaryocytes and platelets, although new patterns also emerged. Among 7 conserved miRNAs that were upregulated most strongly in megakaryocytes, 6 were also induced in the related erythroid lineage. MiR-146a was strongly upregulated during mouse and human megakaryopoiesis, but not erythropoiesis. However, overexpression of miR-146a in mouse bone marrow hematopoietic progenitor populations produced no detectable alterations in megakaryocyte development or platelet production in vivo or in colony assays. Our findings extend the repertoire of differentially regulated miRNAs during murine megakaryopoiesis and provide a useful new dataset for hematopoiesis research. In addition, we show that enforced hematopoietic expression of miR-146a has minimal effects on megakaryopoiesis. These results are compatible with prior studies indicating that miR-146a inhibits megakaryocyte production indirectly by suppressing cytokine production from innate immune cells, but cast doubt on a different study, which suggests that this miRNA inhibits megakaryopoiesis cell-autonomously.
2010-12-07 | GSE22480 | GEO
Project description:MicroRNAs are small non-coding RNAs that regulate cellular development by interfering with mRNA stability and translation. We defined the kinetics of global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were upregulated and 81 were downregulated. Many of these changes are consistent with miRNA profiling studies of human megakaryocytes and platelets, although new patterns also emerged. Among 7 conserved miRNAs that were upregulated most strongly in megakaryocytes, 6 were also induced in the related erythroid lineage. MiR-146a was strongly upregulated during mouse and human megakaryopoiesis, but not erythropoiesis. However, overexpression of miR-146a in mouse bone marrow hematopoietic progenitor populations produced no detectable alterations in megakaryocyte development or platelet production in vivo or in colony assays. Our findings extend the repertoire of differentially regulated miRNAs during murine megakaryopoiesis and provide a useful new dataset for hematopoiesis research. In addition, we show that enforced hematopoietic expression of miR-146a has minimal effects on megakaryopoiesis. These results are compatible with prior studies indicating that miR-146a inhibits megakaryocyte production indirectly by suppressing cytokine production from innate immune cells, but cast doubt on a different study, which suggests that this miRNA inhibits megakaryopoiesis cell-autonomously. Exiqon locked nucleic acid (LNA) microarrays were used to compare microRNA expression in starting populations (ter 119- progenitors) and purified megakaryocytes. Day13.5-14.5 murine fetal livers (strain CD1) were depleted of erythroid cells and cultured with thrombopoietin to generate megakaryocytes. Each total RNA sample (0.5 μg per reaction) was labeled with Hy3 and Hy5 dyes using the Exiqon Power Labeling Kit and automated microarray hybridizations and washes were performed on a Tecan HS4800 station with 20 hr hybridization at 56ºC. Dye-swap pairs of three replicate experiments comparing Ter119- fetal liver cells vs. BSA-purified megakaryocytes were co-hybridized to six arrays. The geometric average of the 532 and 635 measurements after normalization was determined for each sample.
2010-12-07 | E-GEOD-22480 | biostudies-arrayexpress
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: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:G1ME cells are GATA1-deficient murine bipotential megakaryocyte/erythrocyte progenitor cells derived from Gata1-negative murine ES cells. In order to assess the impact of GATA1 on gene regulation and cell differentiation, an expression construct was used to transiently produce high levels of GATA1. Cells transduced with this construct or a vector control were harvested at 18 and 42 hours, and gene expression was analyzed using Affymetrix MOE430 version 2 arrays.
2009-06-10 | GSE14980 | GEO
Project description:Megakaryocyte derived immunoregulatory cells regulate host-defense immunity against bacterial pathogens
| PRJNA706584 | ENA