Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p 0.0001). At FDR 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence.
Specimen part, Disease
View SamplesPrecise localization of the histone H3 variant CENP-A(Cse4) to centromeres is essential for accurate chromosome segregation. In budding yeast, CENP-A(Cse4) is regulated by ubiquitin-mediated proteolysis to ensure its exclusive localization to the centromere. Overexpression of CENP-A(Cse4) is lethal when the CENP-A(Cse4) E3 ubiquitin ligase, Psh1, is deleted. CENP-A(Cse4) mislocalizes to promoters in this condition, so we investigated if there was an effect on gene expression of downstream genes using RNA-seq. Overall design: RNA-seq from two or three biological replicates each, at t0 and t2 hours after adding galactose for each of 6 experimental genotypes.
Regulation of Budding Yeast CENP-A levels Prevents Misincorporation at Promoter Nucleosomes and Transcriptional Defects.
Subject, Time
View SamplesEngineered abiotic stress resistance is an important target for increasing agricultural productivity.There are concerns, however, regarding possible ecological impacts of transgenic crops. In contrast to the first wave of transgenic crops, many abiotic stress resistance genes can initiate
Comparison of salt stress resistance genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change may not predict secondary phenotypic or fitness effects.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Sex, Specimen part, Time
View SamplescDNA and cRNA hybridization technologies have different, probe-specific sensitivities. We used samples from an etanercept trial (GSE11903) to explore in a real-life setting the uniqueness of each platform.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Specimen part, Time
View SamplesTo explore the psoriasis phenotype and pathways involved in psoriasis, we characterized gene expression in lesional and non-lesional skin from psoriasis patients.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Specimen part
View SamplesTo explore the psoriasis phenotype, we characterize gene expression in lesional and non-lesional skin from psoriasis patients.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Sex, Specimen part
View SamplesNotch activation is instrumental in the development of most T-cell acute lymphoblastic leukemia (T-ALL) cases, yet Notch mutations alone are not sufficient to recapitulate the full human disease in animal models. We here found that Notch1 activation at the fetal liver (FL) stage expanded the hematopoietic progenitor population and conferred it transplantable leukemic-initiating capacity. However, leukemogenesis and leukemic-initiating cell capacity induced by Notch1 was critically dependent on the levels of ß-Catenin in both FL and adult bone marrow contexts. In addition, inhibition of ß-Catenin compromised survival and proliferation of human T-ALL cell lines carrying activated Notch1. By transcriptome analyses, we identified the MYC pathway as a crucial element downstream of ß-Catenin in these T-ALL cells and demonstrate that the MYC 3'' enhancer required ß-Catenin and Notch1 recruitment to induce transcription. Finally, PKF115-584 treatment prevented and partially reverted leukemogenesis induced by active Notch1. Overall design: Four T-ALL cell lines (RPMI8402, HPB-ALL, Jurkat, CCRF-CEM) were treated with DMSO (control) or PKF115-584 (310nM) for 3hrs. Gene expression changes were measured with Cufflinks comparing the 4 control with the 4 treated samples.
β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1.
No sample metadata fields
View SamplesWe have generated a mouse model for tumor initiation carrying a mutation in APC and lacking IKKa in intestinal epithelial cells. IKKa-deficient intestinal cells primarily failed to generate adenomas, and the few adenomas arising in this background displayed a significant reduction in cell proliferation. Using an in vitro model for intestinal tumoroids (derived from adenoma initiating cells), we have performed RNA sequencing of wild type and IKKa-deficient intestinal tumoroids. This has demonstrated that epithelial IKKa controls transcription of stem cell-related genes and genes associated with proliferation and apoptosis. Overall design: RNA sequencing of IKKa WT and KO tumoroids, done in triplicates
IKKα is required in the intestinal epithelial cells for tumour stemness.
Specimen part, Cell line, Subject
View SamplesTransgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
Genome-wide analysis of Polycomb targets in Drosophila melanogaster.
Sex, Age, Specimen part
View Samples