Filters
Technology
Platform
GSE25462
Homo sapiens
48 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) and is even present in offspring of diabetic parents. However, molecular mediators of insulin resistance remain unclear. We find that the top-ranking gene set in expression analysis of muscle from humans with T2D and normoglycemic insulin resistant subjects with parental family history (FH+) of T2D is increased expression of actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator MKL1. Furthermore, the SRF activator STARS is upregulated in FH+ and T2D and inversely correlated with insulin sensitivity. These patterns are recapitulated in insulin resistant mice, and linked to alterations in two other regulators of this pathway: reduced G-actin and increased nuclear localization of MKL1. Both genetic and pharmacologic manipulation of STARS/MKL1/SRF pathway significantly alter insulin action: 1) Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation; 2) reduced STARS expression increased insulin signalling and glucose uptake, and 3) SRF inhibition by CCG-1423 reduced nuclear MKL1, improved glucose uptake, and improved glucose tolerance in insulin resistant mice in vivo. Thus, SRF pathway alterations are a signature of insulin resistance which may also contribute to T2D pathogenesis and be a novel therapeutic target.
Publication Title
Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of genes that were differentially expressed in axolotl extract reprogrammed tumour xenografts compared to untreated controls. The study provided insight into the biological processes, signalling pathways and gene networks affected by the oocyte extract treatment which resulted in halted tumour growth in mice.
Publication Title
Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Indicated cells were subjected to RNAi against linker histone H1, Nautilus (control), or GFP (control). RNA was isolated and subjected to Affymetrix GeneChIP Drosophila Genome 2.0 arrays
Publication Title
Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
Illumina Genome Analyzer II
Description
Salivary glands or larval ovaries were isolated from transgenic flies expressing RNAi targeting Nautilus (control) or linker histone H1 using a Tub-Gal4 driver. Overall design: ~200 larvae were used to isolate salivary glands or ovaries, independently. Total RNA was isolated using Trizol reagent following manufacturer''s guidelines. Then 5 µg of total RNA was separated on a polyacrylamide gel, and 18-29 nt small RNAs were isolated for cloning.
Publication Title
Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 4000
Description
A LHX4 transgenic reporter line with high specificity for developing mouse cone photoreceptors was identified and used to purify early stage cone photoreceptors for profiling by single cell RNA sequencing. Overall design: Collection of FACS-sorted LHX4::GFP+ E14.5 early cones and LHX4::GFP- retinal cells for further analysis.
Publication Title
Identification of Genes With Enriched Expression in Early Developing Mouse Cone Photoreceptors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Gallus gallus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Here we report a transcriptomic analysis of fate-restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate-restricted retinal progenitor cells Overall design: Comparison of two FACS-sorted chick retinal progenitor cell populations after electroporation of reporter plasmids and 20hr culture.
Publication Title
Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Illumina Genome Analyzer
Description
Gene expression is regulated both by cis elements, which are DNA segments closely linked to the genes they regulate, and by trans activating factors, which are usually proteins capable of diffusing to unlinked genes. Understanding the patterns and sources of regulatory variation is crucial for understanding phenotypic and genome evolution. Here, we investigate the global patterns of gene expression evolution in Saccharomyces cerivisiae. We report statistical methods useful in quantifying cis and trans regulation using next generation sequencing data. Using these methods, measured genome-wide allele-specific expression by deep sequencing to investigate the genetic architecture of gene regulatory variation between two strains of Saccharomyces cerevisiae. We find that expression polymorphism in yeast is common for both cis and trans regulation, though trans variation is more common. Our detailed analyses of the effects of functional constraint on expression variation as indicated by measures such as protein connectivity, gene essentiality, and the ratio of nonsynonymous substitutions to synonymous substitutions clearly reveal that both classes of variation are under purifying selection, but trans variation is more sensitive to selective constraint. Comparing interspecific expression divergence between S. cerevisiae and S. paradoxus to our intraspecific variation suggests that natural selection strongly influences the patterns of variation we observe. Further analyses revealed that cis divergence is more frequently mediated by positive Darwinian selection than trans divergence, which is compatible with neutral evolution. Overall design: Study the gene expression patterns in two strains of yeast (BY and RM)
Publication Title
Natural selection on cis and trans regulation in yeasts.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Glucose is the most important metabolic substrate of the retina and maintenance of nor-moglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. We recently showed that hy-poglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression is modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we highlight, by gene set enrichment analysis, three important pathways, including KEGG lysosomes, KEGG GSH metabolism and REACTOME apoptosis pathways. We tested the effect of recurrent hypoglycemia (three successive 5h periods of hypoglycemia separated by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevents retinal cell death and GSH decrease, or adapts the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining normal GSH level, as well as a strict glycemic control, may represent a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.
Publication Title
Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The establishment of ad/abaxial polarity is a fundamental event in plant development. It is critical for correct polar development of the leaf (the upper portion of the leaf is chloroplast rich and optimized for light capture while the lower portion is optimized for gas exchange) and for creating an environment that allows the formation of new meristems (centers of stem cell growth). Class III homeodomain-leucine zipper (HD-ZIPIII) proteins are conserved plant proteins that act as potent regulators of ad/abaxial polarity. HD-ZIPIII protein activity promotes the development of upper (adaxial) leaf fates and meristem formation; in its absence lower (abaxial) leaf fates develop and meristems fail to form. A network of regulatory factors controls the establishment of ad/abaxial leaf fates. However, this network is incomplete and how these factors control one another is poorly understood. Here we report a new family of plant genes, the LITTLE ZIPPER (ZPR) genes (consisting principally of a stretch of leucine zipper similar to the leucine zipper in HD-ZIPIII proteins) that are transcriptionally up-regulated by HD-ZIPIII activity. Furthermore, we show that the ZPR proteins interact with and repress HD-ZIPIII activity, thus forming a negative feedback loop. Our results suggest that HD-ZIPIII proteins exist in active homodimers and, together with the ZPR proteins, in inactive heterodimers. The newly discovered HD-ZIPIII/ZPR regulatory module would not only serve to dampen the effect of fluctuations in HD-ZIPIII protein levels but more importantly would provide a point of regulation - control over the ratio of inactive heterodimers to active homodimers - that could be influenced by other components of the pathway. For instance, the binding of a small hydrophobic molecule to the conserved (yet little understood) START domain present in the HD-ZIPIII proteins may influence the type of dimer formed.
Publication Title
A feedback regulatory module formed by LITTLE ZIPPER and HD-ZIPIII genes.
Sample Metadata Fields
No sample metadata fields
View Samples