MicroRNA expression profile of platelets in sickle cell disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41574 | GEO | 2013/06/20
SECONDARY ACCESSION(S): PRJNA177573
REPOSITORIES: GEO
Similar Datasets
Project description:Circulating platelets from Sickle cell disease (SCD) patients express distinct gene expression patterns that regulate function. The objective of this study is to identify a role of post-transcriptional regulation of the platelet transcriptional signaling by microRNAs. Comparison of microRNA expression in platelets from SCD patients and control subjects, from 2 cohorts-University of Pittsburgh and National Institutes of Health.
2013-06-20 | E-GEOD-41574 | biostudies-arrayexpress
Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Experiment Overall Design: There are 18 sickle cell samples and 12 control samples from healthy African American volunteers.
2008-06-18 | E-GEOD-11524 | biostudies-arrayexpress
Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Keywords: Platelets, genes, enzymes, metabolism, signal transduction, sickle cell disease
2008-05-22 | GSE11524 | GEO
Project description:Clinical variability in sickle cell disease (SCD) suggests a role for extra-erythrocytic factors in the pathogenesis of vasoocclusion. We hypothesized that one potential factor, endothelial dysfunction, results from induction of phenotypic changes by circulating factors in SCD patients. The database reports gene expression in cultured human pulmonary artery endothelial cells (HPAEC) exposed to plasma from: a) sickle acute chest syndrome (ACS) patients (samples ; b) SCD patients at steady-state and c) normal volunteers using microarrays (U133A-B GeneChip Affymetrix).
2007-08-25 | E-GEOD-1849 | biostudies-arrayexpress
Project description:Clinical variability in sickle cell disease (SCD) suggests a role for extra-erythrocytic factors in the pathogenesis of vasoocclusion. We hypothesized that one potential factor, endothelial dysfunction, results from induction of phenotypic changes by circulating factors in SCD patients. The database reports gene expression in cultured human pulmonary artery endothelial cells (HPAEC) exposed to plasma from: a) sickle acute chest syndrome (ACS) patients (samples ; b) SCD patients at steady-state and c) normal volunteers using microarrays (U133A-B GeneChip Affymetrix). Keywords: other
2005-04-04 | GSE1849 | GEO
Project description:Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated vascular injury and tissue damage. Classical monocytes (CMo), which comprise most blood circulating monocytes. are activated in SCD, but the cause and consequences of activation is less clear. Using transcriptome analysis, we found upregulation of the type I Interferon (IFN) pathway in sort-purified SCD CMo.
2021-11-10 | GSE168532 | GEO
Project description:Thrombopoietin (TPO) acting via its receptor Mpl is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets (MplPF4cre/PF4cre). MplPF4cre/PF4cre mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential progenitor cells, the latter displaying biological responses and a gene expression signature indicative of chronic TPO over-stimulation as the underlying causative mechanism, despite a normal circulating TPO level. Thus, TPO signaling in megakaryocytes is dispensable for platelet production; its key role in control of platelet number is via generation and stimulation of the bipotential megakaryocyte precursors. Nevertheless, Mpl expression on megakaryocytes and platelets is essential to prevent megakaryocytosis and myeloproliferation by restricting the amount of TPO available to stimulate the production of megakaryocytes from the progenitor cell pool.
2014-06-10 | E-MTAB-2389 | biostudies-arrayexpress
Project description:Sickle cell disease (SCD) is caused by a pathogenic hemoglobin (Hb) mutation, yet patients can have dramatically variable clinical manifestations. Here we address the genetic basis of this clinical heterogeneity. Using a systems genetics approach, we performed whole blood gene expression analysis and eQTL analysis on different clinical phenotypes in SCD patients. We generated whole blood gene expression profiles for 311 West-African children recruited from the National Sickle Cell Disease Centre in Cotonou, Benin which included 250 patients with varying degrees of SCD severities and 61 age-matched controls. SCD is caused by a point-mutation in the beta-hemoglobin gene that changes the normal HbAA protein into, most often, an abnormal HbSS or HbSC protein. The SCD patients recruited in the study either had HbSS or HbSC phenotypes and were categorized into different 3 clinical states based on follow-up status (Rahimy, MC, et al. Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in sub-Saharan African setting. Bood 102, 834-838. 2002). When patients are refered to the clinic, they are enrolled when they are in steady-state condition, and are labeled as entry (E). Patients followed at the SCD clinic are labeled as FU. Control patients were recruited and are labeled as C. Patients were also assigned a severity score (Sebastiani, P. et al. A network model to predict the risk of death in sickle cell disease. Blood 110, 2727-2735, 2007). Hemoglobin protein status (Hb phenotype) was confirmed for each patient using standard electrophoretic techniques. We generated genotypes for 263 of these individuals and performed principal component analysis (PCA) which identified 2 signigicant genotypic principal components (gPC1 and gPC2). Using the gene expression and genotyping data, we performed an eSNP analysis. . Gene expression data presented in this study.
2014-07-01 | E-GEOD-35007 | biostudies-arrayexpress
Project description:Sickle cell disease is associated with systemic complications, many associated with either severity of disease or increased risk of mortality. We sought to identify a circulating gene expression profile whose predictive capacity spanned the spectrum of these poor outcomes in sickle cell disease. The Training cohort consisted of patients with SCD who were prospectively recruited from the University of Illinois. The Testing cohort consisted of a combination of patients prospectively seen at two separate institutions including the University of Chicago and Howard University
2017-09-08 | GSE84632 | GEO
Project description:Sickle cell disease is associated with systemic complications, many associated with either severity of disease or increased risk of mortality. We sought to identify a circulating gene expression profile whose predictive capacity spanned the spectrum of these poor outcomes in sickle cell disease. The Training cohort consisted of patients with SCD who were prospectively recruited from the University of Illinois. The Testing cohort consisted of a combination of patients prospectively seen at two separate institutions including the University of Chicago and Howard University.
2017-09-08 | GSE84633 | GEO