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GSE13381
Rattus norvegicus
6 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The aim of the present study was to explore the transcriptome of pancreatic islets and, based on this information, to prepare a comprehensive and open access inventory of insulin-producing -cell gene expression, the beta-Cell Gene Atlas (BCGA).
Publication Title
Detailed transcriptome atlas of the pancreatic beta cell.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 179 Downloadable Samples
Illumina HiSeq 2000
Description
Progressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes. Overall design: Five independent preparations of EndoC-ßH1 cells exposed to control (siCTL) or SRp55 (siSR#2) siRNAs
Publication Title
SRp55 Regulates a Splicing Network That Controls Human Pancreatic β-Cell Function and Survival.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina Genome Analyzer II
Description
We have used RNA-seq to identify transcripts, including splice variants, expressed in human islets of Langerhans under control condition or following exposure to the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interferon-? (IFN-?). A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets. 25/41 of the candidate genes for type 1 diabetes are expressed in islets, and cytokines modified expression of several of these transcripts. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)
Publication Title
Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Publication Title
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
In the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Publication Title
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)
Publication Title
RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2500
Description
We show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
Publication Title
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The transcription factor B Cell CLL/Lymphoma 11B (BCL11B) is indispensable for T lineage development of lymphoid progenitors. Here we show that chimeric antigen receptor (CAR) expression early in ex vivo generated lymphoid progenitors suppresses Bcl11b, leading to suppression of T cell-associated gene expression and acquisition of natural killer (NK) cell-like properties. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene-expression and inform the potential use of ex vivo generated CARiK cells as a broadly applicable product for targeted immunotherapy.
Publication Title
Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development.
Sample Metadata Fields
Specimen part, Cell line
View Samples