Filters
Technology
Platform
GSE146615
Homo sapiens
144 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential response in gene expression to high glucose in lymphoblastoid cell lines derived from matched type 1 diabetic individuals with and without retinopathy. Those genes exhibiting the largest difference in glucose response between diabetic subjects with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a meta-genome-wide association study. All genetic variants associated with gene expression (expression QTLs; eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the glucose response gene eQTLs among small association p-values for diabetic retinopathy. Among these, we identified FLCN as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose is greater in individuals with diabetic retinopathy compared to diabetic individuals without retinopathy. Three large, independent cohorts of diabetic individuals revealed an enhanced association of FLCN eQTL to diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy in diabetic individuals. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene in diabetic retinopathy.
Publication Title
Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
3T3-L1 adipocytes were treated inhibitors against the glutathione and thioredoxin cycling pools for several time-points (2-24 h).
Publication Title
The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
3T3-L1 adipose cells were grown, differentiated and insulin resistance was stimulated by addition of Glucose Oxidase.
Publication Title
The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model.
Publication Title
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity. Overall design: We examined the transcriptional profile in control and RNaseH1 overexpression mouse ES cells during differentiation.
Publication Title
R loops regulate promoter-proximal chromatin architecture and cellular differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse pancreas from wild type and MistKO animals were induced either with caerulein or saline as control and processed for RNA. Targets from three biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Expression chips 430. Comparisons between the sample groups allow the identification of genes with differential expression patterns of genes which might contribute to pancreatitis.
Publication Title
Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Approximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, most noncoding RNA (ncRNA) is rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from approximately 57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions both to keep NDRs nucleosome-free and to promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near an NDR using a nucleosome-positioning sequence, we find that esBAF is no longer required to silence transcription. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs. Overall design: Examine nucleosome occupancy (MNase-Seq) and transcript production (CapSeq and RNA-Seq) in EGFP KD and Smarca4 KD ESCs
Publication Title
Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Decidualization is a critical process for embryo implatation during which uterine stromal fibroblasts are transformed into large, epithelioid-like decidual cell. NOTCH1 is recepotor of Notch signaling that plays important roles for cell-cell communication, which involves gene regulatory mechanisms that control multiple cellular differentiation processes during embryonic and adult life.
Publication Title
Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Mice were immunized with PCC (pigeon cytochrome c).
Publication Title
Lymphoid reservoirs of antigen-specific memory T helper cells.
Sample Metadata Fields
No sample metadata fields
View Samples