This SuperSeries is composed of the SubSeries listed below.
Tissue-specific genetic control of splicing: implications for the study of complex traits.
Sex, Age
View SamplesNumerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes.
Tissue-specific genetic control of splicing: implications for the study of complex traits.
Sex, Age
View SamplesNumerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes.
Tissue-specific genetic control of splicing: implications for the study of complex traits.
Sex, Age
View SamplesOur earlier study demonstrated that when CFSE-labeled LCMV-or Pichinde virus-immune spleen leukocytes were transferred into T cell-deficient hosts, the bona fide virus-specific memory cells underwent relatively limited cell division and were substantially diluted in frequency by other more extensively proliferating cells originating from that donor cell population. We questioned how the slowly dividing population, which contained bona fide memory cells, differed from the rapidly dividing cells, which contained memory-like cells. As a preliminary screen we performed a comparative genome-wide microarray analysis of genes expressed on sorted rapidly proliferating (CFSE-low) and slowly proliferating (CFSE-high) CD8 cell populations
Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation.
Age, Specimen part
View SamplesThe Her-2/Neu-positive mouse breast cancer cell line was serially co-cultured with minced brain, bone marrow, and lung tissue in an intravital microscopy chamber mounted on the dorsal skinfold of nude mice, alternating with growth in vitro. Gene expression analysis was performed on the cells grown in culture after sorting and further growth in vitro. Gene expression under these growth conditions differed in time and according to the co-cultivated organ tissue. This study reveals genes that are expressed by cells as they adapt differentially to various foreign tissue microenvironments, and may represent a paradigm to discover gene expression changes that occur immediately upon extravasation when cancer metastasizes.
Effects of different tissue microenvironments on gene expression in breast cancer cells.
Cell line
View SamplesThe mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex.
Gene expression profile in rat adrenal zona glomerulosa cells stimulated with aldosterone secretagogues.
No sample metadata fields
View SamplesMycobacterium bovis (M. bovis) and Mycobacterium avium subspecies paratuberculosis (MAP) are important pathogens of cattle, causing bovine tuberculosis and Johne's disease respectively. M. bovis and MAP infect residential macrophages in the lung and intestines respectively and subvert the macrophage biology to create a survival niche. To investigate this interaction we simultaneously studied the transcriptional response of bovine monocyte-derived macrophages to infection with two strains of M. bovis (AF2122/97 and G18) and two strains of MAP (C & L1). Overall design: 120 samples were analysed in total; derived from six biological replicates (i.e. cells isolated from six cattle). Cells were left uninfected (medium only controls) or infected with either a M. bovis strain (AF2122/97 or G18) or a MAP strain (C or L1). Cells were harvested at 2, 6, 24 and 48h post infection.
Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom.
Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
No sample metadata fields
View SamplesIn addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines.
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
No sample metadata fields
View SamplesIn addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha mutant (ERalpha 203/204/211E) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERalpha are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERalpha signaling in model cell lines.
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
No sample metadata fields
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