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SRP075806
Homo sapiens
116 Downloadable Samples
Description
Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). Obesity is tightly associated with T2D, making it challenging to isolate specific effects attributed to the disease alone. By using an in vitro myocyte model system we were able to isolate the inherent properties retained in myocytes originating from donor muscle precursor cells, without being confounded by varying extracellular factors present in the in vivo environment of the donor. We generated and characterized transcriptional profiles of myocytes from 24 human subjects, using a factorial design with two levels each of the factors T2D (healthy or diseased) and obesity (non-obese or obese), and determined the influence of each specific factor on genome-wide transcription. We identified a striking similarity of the transcriptional profiles associated independently with T2D or obesity. Obesity thus presents an inherent phenotype in skeletal myocytes, similar to that induced by T2D. Through bioinformatics analysis we found a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating the observed transcriptional signatures. Functional characterization of the expression profiles revealed dysregulated myogenesis and down-regulated muscle function in connection with T2D and obesity, as well as up-regulation of genes involved in inflammation and the extracellular matrix. Further on, we identified a metabolite subnetwork involved in sphingolipid metabolism and affected by transcriptional up-regulation in T2D. Collectively, these findings pinpoint transcriptional changes that are hard-wired in skeletal myocytes in connection with both obesity and T2D. Overall design: Isolated skeletal muscle precursor cells from 24 males and females (6 normal glucose tolerant, 6 obese, 6 type 2 diabetic, and 6 obese and type 2 diabetic) were differentiated in vitro and stimulated with insulin. RNA from fully differentiated myotubes sampled at 0, 0.5, 1, and 2 hours after insulin stimulation was quantified using RNA-seq (96 samples in total). The 6 base-line (0h) samples from normal glucose tolerant individuals are available under the submission GSE63887, the remaining 90 samples are contained in this submission.
Publication Title
Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Skeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D. Overall design: Isolated skeletal muscle precursor cells from six normal glucose tolerant and non-obese males and females were differentiated in vitro. RNA from fully differentiated myotubes was sequenced using RNA-seq.
Publication Title
Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA sequencing data for four cell lines representing different stages during malignant transformation.
Publication Title
Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing the surrounding vasculature network. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines responded strikingly different to hypoxia. We demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response. Overall design: 16 paired-end samples in total: 4 different cell lines sequenced in duplicate across 2 conditions each.
Publication Title
Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the possible targets in EMT-acquisition after developing acquired platinum resistance in urothelial carcinoma (UC), we examined the changes in global gene expression before and after development of acquired platinum resistance. Comparing two types of acquired platinum resistant UC cells and their corresponding parent cells, in the end we identified 49 genes (25 up-regulated and 24 down-regulated genes) which were commonly changed in two acquired platinum resistant UC cells.
Publication Title
Acquired platinum resistance involves epithelial to mesenchymal transition through ubiquitin ligase FBXO32 dysregulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The instrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterised. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts with only minor fluctuations over time in culture (from day 15 to day 48).
Publication Title
Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Foxl2 is a forkhead transcription factor expressed only in the female, but not in the male gonad. We have created mice homozygous mutant for the Foxl2 gene (KO) as well as mice carrying a conditional mutant Foxl2 allele (floxed).
Publication Title
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
GRBATKO_BAT_COLDEXPOSURE
Publication Title
The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The myogenic regulatory factor MRF4 is expressed at high levels in myofibers of adult skeletal muscle, but its function is unknown. Here we show that knockdown of MRF4 in adult muscle causes hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and the widespread activation of genes involved in muscle contraction, excitation-contraction coupling and energy metabolism, many of which are known targets of MEF2 transcription factors. Genes regulated by MEF2 represent the top-ranking gene set enriched after Mrf4 RNAi, and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The role of MEF2 in mediating the effect of MRF4 knockdown is supported by the finding that Mrf4 RNAi-dependent increase in fiber size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofiber hypertrophy. The nuclear localization of the MEF2 co-repressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. The demonstration that fiber size in adult skeletal muscle is controlled by the MRF4-MEF2 axis opens new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia.
Publication Title
MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Patients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese subjects undergoing bariatric surgery and then used for the mRNA expression analyses. Overall design: mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500.
Publication Title
Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples