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SRP106077
Homo sapiens
207 Downloadable Samples
Illumina HiSeq 2000
Description
Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth retardation, feeding problems, and various congenital malformations. Our combined clinical and molecular data define the 'YY1 syndrome' as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from person-derived cells, using antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding, with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators. Overall design: Individuals with mutations or deletion in YY1 were identified among patients with idiopathic intellectual disability. LCLs were established from 4 of these patients (1 deletion, 2 missense mutations, and 1 non-sense mutation undergoing non-sense-mediated decay) as well as from unrelated controls, and their transcriptome were compared.
Publication Title
YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Voluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma
Publication Title
Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Global gene expression in TET2 mutant and Wild type patients. We performed an integrated analysis of global DNA methylation and gene expression data to investigate the effects of DNA hypermethylation on gene expression.
Publication Title
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG binding protein 2. MeCP2 is a transcriptional repressor elevated in mature neurons and is predicted to be required for neuronal maturation by regulating multiple target genes. Identifying primary gene targets in either Mecp2-deficient mice or human RTT brain has proven to be difficult, perhaps because of the transient requirement for MeCP2 during neuronal maturation. In order to experimentally control the timing of MeCP2 expression and deficiency during neuronal maturation, human SH-SY5Y cells undergoing mature neuronal differentiation were transfected with methylated MeCP2 oligonucleotide decoy to disrupt the binding of MeCP2 to endogenous targets. Genome-wide expression microarray analysis identified all four known members of the inhibitors of differentiation or inhibitors of DNA binding (ID1, ID2, ID3 and ID4) subfamily of helix-loop-helix (HLH) genes as novel neuronal targets of MeCP2. Chromatin immunoprecipitation analysis confirmed binding of MeCP2 near or within the promoters of ID1, ID2 and ID3, and quantitative RT-PCR confirmed increased expression of all four Id genes in Mecp2-deficient mouse brain. All four ID proteins were significantly increased in Mecp2-deficient mouse and human RTT brain using immunofluorescence and laser scanning cytometric analyses. Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT.
Publication Title
Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Uterine tissue is highly responsive to estrogen, which plays a mayor role in sympathetic innervation remodeling in myometrium
Publication Title
Neurotrimin is an estrogen-regulated determinant of peripheral sympathetic innervation.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Exponentially growing cells and type II persister cells from the DS1-(hipQ)-strain
Publication Title
Novel protocol for persister cells isolation.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Macaca mulatta
- 5 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix.
Publication Title
Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons.
Sample Metadata Fields
Cell line
View Samples