Transcriptomic profiling of dorsal root ganglia of transgenic sickle and control mouse models for studying genetic signatures of pain in sickle cell disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE86418 | GEO | 2017/04/05
SECONDARY ACCESSION(S): PRJNA341718
REPOSITORIES: GEO
Similar Datasets
Project description:To date, little is known about lung disease pathogenesis in patients with sickle cell disease (SCD). Acute chest syndrome (ACS) is a significant cause of morbidity and premature.mortality in SCD, but preventative, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) can have overlapping features such as chest pain, which causes a diagnostic dilemma for clinicians. We aimed to explore changes in gene expression profiles in patients with SCD at baseline and during hospitalization for VOC or ACS in order to better understand ACS disease pathogenesis.
2019-11-05 | GSE139912 | GEO
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: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:Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)–like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell–derived erythroid progenitors. We investigated the ability of dimethyl fumarate (DMF), a small-molecule Nrf2 agonist, to activate γ-globin transcription and enhance HbF in tissue culture, murine and primate models. DMF recruited Nrf2 to the γ-globin promoters and the locus control region of the β-globin locus in erythroleukemia cells, elevated HbF in SCD donor–derived erythroid progenitors, and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice induced HbF and increased Nrf2-dependent genes to detoxify heme and limit inflammation. This improved hematological parameters, reduced plasma-free Hb, and attenuated inflammatory markers. Chronic DMF administration to nonanemic primates increased γ-globin mRNA in BM and HbF protein in red cells. DMF represents a potential therapy for SCD to induce HbF and augment vasoprotection and heme detoxification
2017-11-01 | GSE105035 | GEO
Project description:Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.
2022-09-03 | GSE212603 | GEO
Project description:Sickle cell disease (SCD) is a devastating hemoglobinopathy prevalent in Chhattisgarh and other states of central India. Clinical features in SCD arise mainly due to anemia and vaso-occlusion and inflammation leading to gradual multiple organ failure. Vaso-occlusive crisis (VOC) is a common cause of sudden death among SCD patients. Aim of the study was to evaluate gene expression in patients of SCD in a quest to search up-regulated genes in VOC.
2017-06-30 | GSE72999 | GEO
Project description:To determine gene expression in humanized SCD Berkeley lung compared to WT control lung
2020-02-10 | GSE114709 | GEO
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:<p>Sickle cell disease (SCD) is a severe debilitating hematological disorder associated with a high degree of morbidity and mortality. There are approximately 200,000 babies born with sickle cell disease each year, with the disease predominately affecting individuals in Africa. The overall global burden of the disease is tremendous, with more than 100,000 patients currently in the US and further millions worldwide. The governing bodies of the World Health Organization have recently adopted a resolution to strengthen the response to sickle disease in all affected countries and there is a definite need for high quality sickle cell disease research that has the potential to improve the treatment and prognosis of patients with this devastating disease. The clinical manifestations of SCD arise from a complex pathophysiology that includes hemolysis, acute vaso-occlusion, endothelial dysfunction, inflammation, and chronic organ damage. While the individual clinical course of this disease is highly variable, many of the associated complications demonstrate some degree of heritability. Intensive research into identifying genetic modifiers that can affect the pathophysiology of SCD has been limited to date and there is an urgent need to improve of our knowledge the molecular mechanisms underlying the clinical complications of SCD. The Sickle cell CIP project is investigating complication of stroke and pharmacogenomics of hydroxyurea response in patients with sickle cell anemia. The major benefit of hydroxyurea comes from its ability to induce fetal hemoglobin (HbF) and higher HbF levels are associated with reduced morbidity and mortality in SCA patients. We will perform whole exome and whole genome sequencing of SCA patients in order to identify genome variants associated with incidences of stroke and HbF response to hydroxyurea.</p>
| phs000691 | dbGaP