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GSE79224
Rattus norvegicus
20 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Complement inhibitor C4b-binding protein (C4BP) is synthesized in liver and pancreas and composed of 7 identical alpha chains and one unique beta chain. We showed previously that C4BP binds islet amyloid polypeptide (IAPP) and affects fibril formation in vitro. Now we found that polymeric C4BP inhibited lysis of human erythrocytes incubated with monomeric IAPP while no erythrocyte lysis was observed after incubation with preformed IAPP fibrils. In contrast, monomeric alpha chain of C4BP had significantly reduced activity. Further, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in decreased cell viability, which was restored in the presence of physiological concentrations of C4BP. Accordingly, addition of C4BP rescued the ability of INS-1 cells and isolated rat islets to respond to glucose stimulation with insulin secretion, which was impaired in the presence of IAPP alone. C4BP was internalized together with IAPP into INS-1 cells and therefore we aimed to study its effect on gene expression. Pathway analyses of mRNA expression microarray data indicated that cells exposed to C4BP and IAPP in comparison to IAPP alone increased expression of genes involved in cholesterol synthesis. Depletion of cholesterol through methyl--cyclodextrin or cholesterol oxidase abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells. Also, inhibition of phosphoinositide 3-kinase but not NF-B had a similar effect. Taken together, one of the mechanisms by which C4BP protects beta-cells from IAPP cytotoxicity is by enhancing cholesterol synthesis.
Publication Title
C4b-binding Protein Protects β-Cells from Islet Amyloid Polypeptide-induced Cytotoxicity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoiesis occurs in a microenviroenment in which stromal cells are prominent. Stromal cells have been shown to maintain stem cell behaviour of hematopoietic stem cells. We derived several different stromal cell lines from midgestation embryos which will, or will not maintain hemetopoietic stem cells in cultures.
Publication Title
Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 128 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models.
Publication Title
The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TCF7L2 is a master regulator of insulin production and processing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we harnessed the potential of expression arrays in 89 human pancreatic islet donors (different levels of blood glucose (HbA1c)) to identify genes regulated in this relevant tissue for type 2 diabetes (T2D).
Publication Title
TCF7L2 is a master regulator of insulin production and processing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability.
Publication Title
A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A gene co-expression network analysis has been conducted to identify T2D-associated gene modules. Donors 1-48 were used for the initial analysis and donors 49-80 for the replication and were normalized separately in this study
Publication Title
Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Publication Title
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The therapeutic potential of pro-resolution factors in determining the outcome of inflammatory events has gained ground over the past decade. However, the attention has been focused on the non-genomic effects of these endogenous, anti-inflammatory substances. In this study, we have focused our attention on identifying specific annexin 1 (AnxA1) protein/ALX receptor mediated gene activation, in an effort to identify down-stream genomic targets of this well-known, glucocorticoid induced, pro-resolution factor.
Publication Title
Downstream gene activation of the receptor ALX by the agonist annexin A1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Malignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions.
Publication Title
Melanomas prevent endothelial cell death under restrictive culture conditions by signaling through AKT and p38 MAPK/ ERK-1/2 cascades.
Sample Metadata Fields
Specimen part
View Samples