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GSE7891
Rattus norvegicus
6 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Identification of gene expressed in the enriched inner medullary collecting duct cells in rat.
Publication Title
Transcriptional profiling of native inner medullary collecting duct cells from rat kidney.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The goal of this study was to identify genes which are differentiatlly expresesd upon induced inactivation of Rfx6 in beta cell in adult mice Overall design: Rfx6fl/fl; Ins1-CreERT2 (mut) and Rfx6fl/fl (ctrl) 8 weeks old mice were injected subcutaneously with tamoxifen daily during 3 days. Pancreatic islets were isolated 5 days after the first injection and RNA purified.
Publication Title
Rfx6 maintains the functional identity of adult pancreatic β cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2500
Description
Individual organisms age at different rates, however, it remains unclear how aging alters the properties of individual cells. Here we show that zebrafish pancreatic beta-cells exhibit heterogeneity in both gene expression and proliferation with age. Individual beta-cells show marked variability in transcripts involved in endoplasmic reticulum stress, inhibition of growth factor signaling and inflammation, including NF-kB signaling. Using a reporter line, we show that NF-kB signaling is indeed activated heterogeneously with age. Notably, beta-cells with higher NF-kB activity proliferate less compared to neighbors with lower activity. Furthermore, NF-kB-signalinghigh beta-cells from younger islets upregulate socs2, a gene naturally expressed in beta-cells from older islets. In turn, socs2 can inhibit proliferation cell-autonomously. NF-kB activation correlates with the recruitment of tnfa-expressing immune cells, pointing towards a role for the islet microenvironment in this activity. We propose that aging is heterogeneous across individual beta-cells and identify NF-kB signaling as a marker of heterogeneity. Overall design: We used fluorescence-activated cell sorting (FACS) coupled with next generation RNA-Sequencing to profile beta-cells from 3 month post fertilization and 1 year post fertilization animals. total RNA was extracted from FACS sorted beta-cells using Quick-RNA MicroPrep kit (R1050 Zymo Research). Sequencing was performed on llumina HiSeq2500 in 2x75bp paired-end mode. Reads were splice-aligned to the zebrafish genome, GRCz10, using HISAT2. htseq-count was used to assign reads to exons thus eventually getting counts per gene.
Publication Title
Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples.
Publication Title
Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Pancreatic beta cells use electrical signals to couple changes in blood glucose concentration to insulin release via extracellular calcium (Ca2+) influx. Sorcin (SRI) is a Ca2+-binding protein whose overexpression in cardiomyocytes rescues the abnormal contractile function of the diabetic heart.
Publication Title
Sorcin Links Pancreatic β-Cell Lipotoxicity to ER Ca2+ Stores.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Peroxisome proliferator-activated receptor beta/delta protects against obesity by reducing dyslipidemia and insulin resistance via effects in various organs, including muscle, adipose tissue, liver, and heart. However, nothing is known about the function of PPAR-beta in pancreas, a prime organ in the control of glucose metabolism. To gain insight into so far hypothetical functions of this PPAR isotype in insulin production, we specifically ablated Ppar-beta in pancreas. The mutated mice developed a chronic hyperinsulinemia, due to an increase in both beta-cell mass and insulin secretion. Gene expression profiling indicated a broad repressive function of PPAR-beta impacting the vesicular compartment, actin cytoskeleton, and metabolism of glucose and fatty acids. Analyses of insulin release from the islets revealed an increased second-phase glucose-stimulated insulin secretion. Higher levels of PKD, PKC-delta and diacyglycerol in mutated animals lead to an enhanced formation of trans-Golgi network (TGN)-to-plasma-membrane transport carriers in concert with F-actin disassembly, which resulted in increased insulin secretion and its associated systemic effects. Taken together, these results provide evidence for PPAR-beta playing a repressive role on beta-cell growth and insulin exocytosis, which shed new light on its anti-obesity action.
Publication Title
PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 383 Downloadable Samples
- Illumina HiSeq 2000
Description
Defective insulin secretion by pancreatic ß cells underlies the development of type 2 diabetes (T2D). High fat diet-fed mice are commonly used to study diabetes progression, but studies are usually limited to a single strain, such as C57Bl/6J. Here, we use a systems biology approach to integrate large phenotypic and islet transcriptomic data sets from six commonly used strains fed a high fat or regular chow diet to identify genes associated with glucose intolerance and insulin secretion. One of these genes is Elovl2, encoding very long chain fatty acid elongase 2. ELOVL2 is responsible for the synthesis of the polyunsaturated fatty acid, docosahexaenoic acid (DHA). We show that DHA rescues glucose-induced insulin secretion and cytosolic Ca2+ influx impaired by glucolipotoxicity, and that Elovl2 over-expression is able to restore the insulin secretion defect under these conditions. We propose that increased endogenous DHA levels resulting from Elovl2 up-regulation counteracts the insulin secretion defect associated with glucolipotoxicity. Although we focus our experimental validation on Elovl2, the comprehensive data set and integrative network model we used to identify this candidate gene represents an important novel resource to dissect the molecular aetiology of ß cell failure in murine models. Overall design: 6 mouse strains, 4 time points, 2 diets
Publication Title
Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Lipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, activate the ATF3 stress pathway, induce secretion of inflammatory cytokines, and increase APP. Our observations are consistent with neurovascular lipotoxicity that could play a role in cognitive decline with aging.
Publication Title
Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
To identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Overall design: Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.
Publication Title
Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 200 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.
Sample Metadata Fields
Age
View Samples