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GSE26637
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
5 arrays from obese insulin-resistant and lean insulin-sensitive females adipose tissue at fasting and after 3h hyperinsulinemia
Publication Title
Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
NextSeq 500
Description
Maintaining metabolic homeostasis in response to fluctuating nutrient intake requires intricate coordination between tissues of multicellular animals. The insulin/glucagon axis is well known to hormonally coordinate organism-wide carbohydrate metabolism. The ChREBP/Mondo-Mlx transcription factors regulate glycolytic and lipogenic genes locally in hepatocytes and adipocytes, but its role in systemic metabolic homeostasis has remained poorly understood. We demonstrate that Mondo-Mlx controls gene activity in several peripheral tissues of Drosophila melanogaster, where it regulates nutrient digestion and transport as well as carbohydrate, amino acid and lipid metabolism. In addition to directly regulating metabolic genes Mondo-Mlx controls a regulatory network composed of the Activin ligand Dawdle and GLI similar transcription factor Sugarbabe. Dawdle and Sugarbabe contribute to the regulation of a subset of Mondo-Mlx-dependent processes, including sugar-induced de novo synthesis of serine and fatty acids. In summary, our study establishes Mondo-Mlx sugar sensor as a master regulator of organismal metabolic homeostasis upon sugar feeding. Overall design: Control (sug17d/+) and sugarbabe null mutant (sug17d/sug def) third instar larvae were fed control low sugar or high sugar diet and total RNA was extracted from the whole larvae.
Publication Title
Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 350 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 228 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
Samples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 122 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Samples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Publication Title
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- NextSeq 500
Description
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis. Overall design: RNA was isolated from zebrafish heart samples (3 wt and 3 miR-29-sponge) and sequenced.
Publication Title
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We report here that REV-ERBa influences nuclear localization of the glucocorticoid receptor and vice versa. As a consequence these two nuclear receptors influence each others transcriptome. REV-ERBa (Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, Nr3c1) influences similar processes, but is not part of the circadian clock mechanism although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes we studied the interplay between these two nuclear receptors. We found that REV-ERBa competes with GR for binding to HSP90, a chaperone responsible for the activation of substrate proteins to ensure survival of a cell. This competition affected stability and nuclear localization of GR, thereby affecting GR target gene expression such as I?B and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence each others transcritpional potential indicating that the transcriptional landscape is strongly dependent on dynamic processes at the protein level. Overall design: In this dataset, we isolated livers at Zeitgebertime (ZT) 8 and ZT20 of wild type and Rev-erb alpha knock-out animals. Liver samples were immediately flash frozen in liquid N2 and stored at -80?°C. RNA was extracted using NucleoSpin RNA (Machery-Nagel, Düren, Germany) according to the instructions of the manufacturer. Quality of the RNA samples was analysed with a spectrophotometer, agarose gel electrophoresis and reverse transcription-PCR. Library construction starting from the poly(A)-tail and multiplexing was performed according to the instructions of the manufacturer (Illumina). The samples were organized as follows: Three replicas (1-WT, 2-WT, 3-WT) correspond to genotype WT at ZT8. Three replicas (4-Rev, 5-Rev, 6-Rev) correspond to genotype Rev-/- at ZT8. Three replicas (7-WT, 8-WT, 9-WT) correspond to genotype WT at ZT20. Three replicas (10-Rev, 11-Rev, 12-Rev) correspond to genotypeRev-/- at ZT20. For the experiment, complementary DNA (cDNA) libraries were barcoded using Illumina primers and loaded onto one lane of an IlluminaHS2000 machine. cDNA libraries were diluted and loaded onto each lane. The samples were sequenced for a maximum sequencing length of 75?bp. Sequences were aligned to the mouse genome (UCSC version mm10 database). Numbers of the sequences obtained for each library can be found in Supplementary Table 3. Sequences (fastq format) were mapped with Tophat (Trapnell, C. 2009), uniquely mapped sequences from the output files (bam format) were then used for further analysis, percentage of the mapping obtained for each sample can be found in Supplementary Table 3. For all files the reads were counted with HTSeq-count using the following criteria: samtools view sample.bam | htseq-count -m union -a 10 -s no -i gene_name Mus_Musculus.gtf > sample_counts.txt Tests for differential expression between the samples were performed in R software (R Core Team, 2014 http://www.R-project.org/) using the DESeq2 package (Version 1.6.3) (Love, M. 2014). A threshold on the corrected P value was used to call for differentially expressed genes (P.adjust<0.05).
Publication Title
REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
We determined genome-wide nucleosome occupancy in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell type and protein specific binding preferences of transcription factors to sites with either low (e.g. Myc, Klf4, Zfx) or high (e.g. Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome depleted regions around transcription start and termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to their CpG-content or histone methylation marks. Throughout the genome nucleosome occupancy was dependent on the presence of certain histone methylation or acetylation modifications. In addition, the average nucleosome-repeat length increased during differentiation by 5-7 base pairs, with local variations for specific genomic regions. Our results reveal regulatory mechanisms of cell differentiation acting through nucleosome repositioning. Overall design: The Total RNA from ESCs, NPCs and MEFs was extracted by guanidinisothiocyanat/phenol extraction with the Trifast kit (Peqlab). Total RNA preparations were treated with DNase I, phenol/chloroform extracted and precipitated before further processing. RNAs were depleted of 5S, 5.8S, 18S and 28S rRNAs using the Human/Mouse/Rat Ribo-Zero rRNA Removal Kit (Epicentre) according to the manufacturer’s protocol. After rRNA depletion, RNAs were fragmented with a kit from Ambion. Libraries for Solexa sequencing were generated according to the standard Illumina protocol that comprised first strand cDNA synthesis, second strand cDNA synthesis, end repair, addition of a single A base, and adapter ligation. Sequencing was performed on the Illumina GAIIx (replicate 1) and Illumina HiSeq 2000 (replicate 2) platforms at the sequencing core facilities of the BioQuant in Heidelberg, Germany. RNA reads were aligned with TopHat. Further expression analysis was with the Genomatix software suite (Genomatix, Munich, Germany) and the Eldorado gene annotation. For each transcript a normalized expression value was calculated from the read distribution that accounts for the length differences using the program DEseq for the analysis of differential expression.
Publication Title
Genome-wide nucleosome positioning during embryonic stem cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch coactivators FRYL and MAML2 were reduced. Gain and loss of function experiments demonstrated that JAG/NOTCH signaling controls sGC expression together with MAML2 and FRYL. Reduced expression of sGC, correlating with differential expression of MAML2 in stroke prone and spontaneously hypertensive rats was also seen and RNA-Seq data demonstrated correlations between JAG1, NOTCH3, MAML2 and FRYL and the sGC subunits GUCY1A3 and GUCY1B3 in human coronary artery. Notch signaling thus provides a constitutive drive on expression of the major nitric oxide receptor (GUCY1A3/GUCY1B3) in arteries from mice, rats, and humans, and this control mechanism is disturbed in hypertension.
Publication Title
Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epidermal stem cells ensure that skin homeostasis is maintained. In murine skin, epidermal stem cells cluster at specific niches where, under steady-state conditions, they undergo cycles of dormancy and activation1. When cellular replenishment is required, epidermal stem cells egress from the niche and proliferate for a limited number of times to subsequently feed into the differentiated compartment1-3. However, only a subset of stem cells becomes active during each round of morphogenesis, suggesting that stem cells coexist in heterogeneous responsive states within the same niche. Using a circadian clock fluorescent reporter mouse model, we show that the dormant epidermal stem cell niche contains two coexisting populations of stem cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. In dormant niches, the core molecular clock protein Bmal1 transcriptionally modulates the expression of stem cell regulatory genes, including modulators of Wnt and TGFb, to create two coexisting stem cell populations, one predisposed, and the other less prone, to activation. Unbalancing this equilibrium of epidermal stem cells, through conditional epidermal deletion of Bmal1, resulted in a long-term progressive accumulation of non-responsive stem cells, premature impairment of tissue self-renewal, and a significant reduction in the development of squamous cell carcinomas. Our results indicate that the molecular clock machinery fine-tunes the spatiotemporal behavior of epidermal stem cells within their niche, and that perturbation of this mechanism affects tissue homeostasis and the predisposition to neoplastic transformation. The goals of this study was to compare the transcriptome of epidermal stem cells according to their circadian rhythm phase. We isolated epidermal stem cells (bulge cells; alpha6bright/CD34+ population) from 19 days old Per1-Venus mice and separated them according to Venusbright (clock positive) and Venus dim (clock negative). The goals of this study was to compare the transcriptome of epidermal stem cells in which their circadian rhythm machinery has been perturbed by deleting the gene that encodes for Bmal1. We compared the transcriptomes of basal interfollicular epidermis cells (alpha6 integrin bright/CD34- cells) from the dorsal skin of 1 year old BmalKO mice and their respective control littermates. Each array corresponds to purified cells from approximately 5 mice.
Publication Title
The circadian molecular clock creates epidermal stem cell heterogeneity.
Sample Metadata Fields
Specimen part
View Samples