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GSE64123
Homo sapiens
90 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Here we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Publication Title
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Loss of function mutations in the transcription factor THAP1 cause DYT6 dystonia, a childhood-onset motor disorder. DYT6 subjects display abnormalities in the white matter regions of the brain.
Publication Title
The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte Lineage.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 188 Downloadable Samples
- Affymetrix Genechip Zebrafish ST Genome Array 1.1 (zebgene11st)
Description
Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
Publication Title
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Publication Title
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
NextSeq 550
Description
WT J1 and 3B3L cells (in which Dnmt3B and Dnm3L are constitutively expressed from an exogenous construct) were cultured under both serum/LIF and 2i/LIF conditions. 3B3L cells do not show ground state-associated hypomethylation phenotype. This experiment sought to analyse the gene expression changes between the two conditions. Overall design: Three biological replicates per condition J1 serum, J1 2i, 3B3-3l serum, 3B3-3l 2i.
Publication Title
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Sus scrofa
- 67 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Background: Marketing products with added-value characteristics is a current trend in livestock production systems. Regarding meat, selection for intramuscular fat and muscular fatty acid composition is a way to improve the palatability and juiciness of meat while assuring a healthy fat content. This represents selecting animal with a different muscular metabolic profile with respect to the extended selection of lean animals. Results: The present study has analysed the muscular gene expression profiles of 68 commercial Duroc pigs belonging to two groups with extreme phenotypes for traits strongly related with lipid deposition and composition. This has allowed us to compare the physiological and metabolic implications of selecting for each of these extreme groups. Rather than upregulation of a single pathway, the main differences lied on the transcriptional levels of genes related with lipogenesis and lipolysis, revealing the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Most strikingly, several genes which enhanced fatty acid -oxidation and favoured insulin signalling and glucose uptake were upregulated in the fattest animals, indicating that the events leading to peripheral insulin resistance in humans with increased levels of intramuscular fat and obesity do not take place in these pigs. Moreover, neither was detected the well-characterised low-grade inflammatory state observed in overweighed humans. Conclusion: As a whole, our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to fully understand how lipid deposition affects muscle physiology in pigs.
Publication Title
Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
TFIID is a central player in activated transcription initiation. Recent evidence suggests that the role and composition of TFIID is more diverse than previously understood. To investigate the effects of changing the composition of TFIID in a simple system we depleted TAF1 from Drosophila cells and determined the consequences on metal induced transcription at an inducible gene, Metallothionein B (MtnB). We observe a marked increase in the levels of both the mature message and pre-mRNA in TAF1 depleted cells. Under conditions of continued metal exposure, we show that TAF1 depletion increases the magnitude of the initial transcription burst, but has no effect on the timing of that burst. We also show that TAF1 depletion causes delay in the shut-off of transcription upon removal of the stimulus. Thus TAFs are involved in both establishing an upper limit of transcription during induction and efficiently turning the gene off once the inducer is removed. Using genomewide nascent-seq we identify hundreds of genes that are controlled in a similar manner indicating that the findings at this inducible gene are likely generalizable to a large set of promoters. There is a long-standing appreciation for the importance of the spatial and temporal control of transcription. Here we uncover an important third dimension of control, the magnitude of the response. Our results show that the magnitude of the transcriptional response to the same signaling event, even at the same promoter, can vary greatly depending on the composition of the TFIID complex in the cell. Overall design: Nascent RNA was sequenced from replicate samples of Drosophila S2 cells treated with double-stranded RNA directed against E. coli LacI (Control) or against Drosophlia TAF1 (experimental). Reads per kilo-base per million (RPKM) was determined for each gene and the control and experimental samples were compared to determine the genes that were affected by the depletion of TAF1.
Publication Title
Holo-TFIID controls the magnitude of a transcription burst and fine-tuning of transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in -tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLB), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; the hearts of these mice exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories show that the hearts of mice that were genetically crossed between the Tm180 and PLB KO mice rescues the hypertrophic phenotype and improves their cardiac morphology and function.
Publication Title
Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
Description
The ubiquitously expressed RNA-binding protein Hu Antigen R (HuR) or ELAVL1 is implicated in a variety of biological processes as well as being linked with a number of diseases, including cancer. Despite a great deal of prior investigation into HuR, there is still much to learn about its function. We take an important step in this direction by conducting iCLIP (CrossLinking and ImmunoPreciptation) and RNA Sequencing experiments followed by an extensive computational analysis to determine the characteristics of the HuR binding site and impact on the transcriptome. We reveal that HuR targets predominantly uracil-rich single-stranded stretches of varying size, with a strong conservation of structure and sequence composition. Despite the fact that HuR sites are observed in intronic regions, our data does not support a role for HuR in regulating splicing. HuR sites in 3'UTRs overlap extensively with predicted miRNA target sites suggesting interplay between the functions of HuR and miRNAs. Network analysis showed that identified targets containing HuR binding sites in the 3' UTR are highly interconnected.
Publication Title
Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex network of target genes and novel characteristics of its binding sites.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Altered Ca2+ handling has both immediate physiological effects and long-term genomic effects on vascular smooth muscle function. Previously we have shown that elevation of cytoplasmic Ca2+ through voltage-dependent Ca2+ channels (VDCCs) or store-operated Ca2+ channels (SOCCs) results in phosphorylation of the Ca2+/cAMP response element binding protein (CREB) in cerebral arteries. Here we demonstrate that stimulation of these different Ca2+ influx pathways results in transcriptional activation of a distinct, yet overlapping set of genes, and that the induction of selected CRE-regulated genes is prevented by the addition of corresponding Ca2+ channel blockers. Using oligonucleotide array analysis, changes in mRNA levels were quantified following membrane depolarization with K+ or depletion of intracellular Ca2+ stores with thapsigargin in human cerebral vascular smooth muscle cells. Array results for differentially regulated genes containing a CRE were confirmed by quantitative RT-PCR, and corresponding changes in protein expression were shown by Western blot analysis and immunofluorescence. Membrane depolarization induced a transient increase in c-fos mRNA and a sustained increase in early growth response-1 (Egr-1) mRNA and protein that were inhibited by application of the VDCC blocker, nimodipine, and the SOCC inhibitor, 2-aminoethoxydiphenylborate (2-APB). Thapsigargin induced a sustained increase in c-fos mRNA and MAP kinase phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by 2-APB but not by nimodipine. Our findings thus indicate that Ca2+ entry through VDCCs and SOCCs can differentially regulate CRE-containing genes in vascular smooth muscle and imply that signals involved in growth modulation are both temporally and spatially regulated by Ca2+.
Publication Title
Ca2+ source-dependent transcription of CRE-containing genes in vascular smooth muscle.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples