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GSE45640
Homo sapiens
82 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic, functional and molecular features of glucocorticoid receptor binding.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 82 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.
Publication Title
Genetic, functional and molecular features of glucocorticoid receptor binding.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 480 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Glucocorticoids (GCs) are steroid hormones produced by the human body in response to environmental stressors. Despite their key role as physiological regulators and widely administered pharmaceuticals, little is known about the genetic basis of inter-individual and inter-ethnic variation in GC response. As GC action is mediated by the regulation of gene expression, we profiled transcript abundance and protein secretion in EBV-transformed B lymphocytes from a panel of 114 individuals, including those of both African and European ancestry. Combining these molecular traits with genome-wide genetic data, we found that genotype-treatment interactions at polymorphisms near genes affected GC-regulation of expression for 26 genes and of secretion for IL6. A novel statistical approach revealed that these interactions could be distinguished into distinct types, with some showing genotypic effects only in GC-treated samples and others showing genotypic effects only in control-treated samples, with differing phenotypic and molecular interpretations. The insights into the genetic basis of variation in GC response and the statistical tools for identifying gene-treatment interactions that we provide will aid future efforts to identify genetic predictors of response to this and other treatments.
Publication Title
Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Sus scrofa
- 90 Downloadable Samples
Illumina HiSeq 2000
Description
We sequenced liver mRNA from 23 individual pigs (5 prefed and 18 fasted) taken at 4 separate time points to evaluate the change in gene expression over the course of hemorrhagic shock and resuscitation in response to a carbohydrate prefed state. Overall design: Examination of mRNA levels in liver biopsies from pigs at 4 timepoints throughout hemorrhagic shock and resuscitation
Publication Title
Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem / progenitor cells for the other airway cell types. The objective of this study is to better understand basal cell biology by defining the subset of expressed genes that characterize the signature of human airway epithelial basal cells.
Publication Title
The human airway epithelial basal cell transcriptome.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Amyotrophic later sclerosis is a motor neuron disease accompanied by metabolic changes. PGC (PPAR gamma coactivator)-1alpha is a master regulator of mitochondrial biogenesis and function and of critical importance for all metabolically active tissues. PGC-1alpha is a genetic modifier of ALS.
Publication Title
ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 114 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
An increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.
Publication Title
Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [HuEx-1_0-st-v2,coreR3,A20071112,EP.cdf (huex10st)
Description
Gene expression profiles of bipolar disorder (BD) patients were assessed during both a manic and a euthymic phase and compared both intra-individually, and with the gene expression profiles of controls.
Publication Title
Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression (mRNA) profiling of human ependymomas
Publication Title
Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- NextSeq 500
Description
Asymmetric cell division results in two distinctly fated daughter cells to generate cellular diversity. A major molecular hallmark of an asymmetric division is the unequal partitioning of cell-fate determinant proteins. We have previously established that growth factor signaling promotes protein depalmitoylation to foster polarized protein localization, which in turns drives migration and metastasis. Here, we report protein palmitoylation as a key mechanism for the asymmetric partitioning of the cell-fate determinants Numb (Notch antagonist) and ß-catenin (canonical Wnt regulator) through the activity of a depalmitoylating enzyme, APT1. Using point mutants, we show specific palmitoylated residues on proteins, such as Numb, are required for asymmetric localization. Furthermore, by live-cell imaging, we show that reciprocal interactions between APT1 and CDC42 regulate the asymmetric localization of Numb and ß-catenin to the plasma membrane. This in turn restricts Notch and Wnt transcriptional activity to one daughter cell. Moreover, we show altering APT1 expression changes the transcriptional signatures to those resembling that of Notch and ß-catenin in MDA-MB-231 cells. We also show loss of APT1 depletes the population of CD44+/CD24lo/ALDH+ tumorigenic cells in colony formation assays. Together, the findings of this study demonstrate that palmitoylation, via APT1, is a major mechanism of asymmetric cell division regulating Notch and Wnt-associated protein dynamics, gene expression, and cellular functions. Overall design: Gene expression by RNAseq of MDA-MB-231 triple receptor negative breast cancer cells expressing scramble control vector, shAPT1 knockdown, and APT1wt performed in triplicate. Total of 9 samples were analyzed.
Publication Title
The depalmitoylase APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples