Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sex, Age, Specimen part
View SamplesCompare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Age, Specimen part
View SamplesThe weaning period consist of a critical postnatal window for structural and physiologic maturation of rat beta cells. To investigate transcriptome changes involved in the maturation of beta cells neighboring this period we performed microarray analysis in FACS beta cell enriched populations to detail the global programme of gene expression to identify its changes during this process.
Transcriptome landmarks of the functional maturity of rat beta-cells, from lactation to adulthood.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, Age, Specimen part
View SamplesMultiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.
Sex, Age, Specimen part, Disease stage, Subject
View SamplesAlthough most cutaneous squamous cell carcinomas (cSCC) develop from actinic keratoses (AK), the key events for this evolution remain unclear. We have combined the results of different genomic and expression array platforms on matched samples of sun-exposed skin, AK and cSCC from ten immunocompetent patients, with the objective of better understanding the mechanisms involved in this progression. Gene expression analysis and copy number alterations were assessed using GeneChip Human Gene 2.0 ST Array (Affymetrix) and CytoScan HD Cytogenetics Solution (Affymetrix) platforms, respectively. Integration of genome and transcriptome results was evaluated using the DR-Integrator tool. Additional studies (qPCR, immunohistochemistry and Western blot) were performed for selected genes. Twenty-two genes showed a progressive expression spectrum from clinically normal sun-exposed skin samples to cSCC. FOSL1 and BNC1 encode transcription factors whose expression was increased in cSCC in the expression array and the qPCR. By immunohistochemistry, FOSL1 showed an intense staining at the invasive front of cSCC samples and BNC1 expression varied from a nuclear location (sun-exposed skin) to a cytoplasmic location (cSCC). Western blot analyses confirmed the enhancement of FOSL1 and BNC1 expression. Additionally, the smallest overlapping regions of genomic imbalance (SORIs) involving at least 3 of the samples of each group (sun-exposed skin, AK or cSCC) were selected. One of the SORIs was a deletion in the p24.1 band of chromosome 3, shared by 7 of the cSCC. A strong correlation in the integration analysis was found for NEK10, a gene contained in the previously mentioned SORI. Loss of NEK10 expression in cSCC was confirmed by immunohistochemistry and western blot analyses. In conclusion, our findings suggest that FOSL1 may play a role in promoting the cSCC invasion ability. We have also identified two additional genes, NEK10 and BNC1, which could also act as tumor drivers.
Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.
Sex, Age, Specimen part, Disease stage, Subject
View SamplesDNA microarray technology is a powerfull tool for genome-wide gene expression analysis of biological samples. Here we review the methodology for expression profiling analysis of skin tissue or purified keratinocytes from mice. We explained the methodology and protocols for RNA preservation and purification, RNA quality and integrity tests, and DNA microarray technology types that can be used. Furthermore, using a dataset of mice samples, we explained how to perform chip raw data preprocessing and normalization, differential expression analysis, as well as gene-clustering and funcional analysis of gene deregulation.
Gene expression profiling of mouse epidermal keratinocytes.
Age, Specimen part
View SamplesWe used Affymetrix microarrays to investigate gene expression changes in PBMCs isolated from male patients ongoing secondary prevention of CVD to determine significant modulatory effects that may have been induced by the intake of an initial dose of 8 mg of resveratrol-enriched grape extract for 6 months and then, 16 mg for a further 6 months.
One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
Sex, Specimen part, Time
View SamplesHuman alveolar epithelial cells were exposed to cigarette smoke extract (CSE) for 1, 3 and 5 weeks at 1%, 5% and 10%, and gene expression was evaluated by complete transcriptome microarrays.
Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.
Cell line, Time
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