Gene expression signatures for human non-diabetic (hND) islets and human type 2 diabetes mellitus (hT2DM) islets
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PROVIDER: PRJNA484689 | ENA |
REPOSITORIES: ENA
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Project description:Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing β-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human β-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased β-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM. Identification of miRNA-target interaction in human islets using HITS-CLIP, one mRNA library and one miRNA library
2013-11-22 | E-GEOD-51924 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing β-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human β-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased β-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM.
2013-11-22 | GSE51924 | GEO
Project description:Type 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo. There are three experiments in this submission. All are in human islets or islet cell types. The first is a comparison of miRNA levels in sorted alpha versus beta cells. There is one replicate for this experiment. The second experiment is to measure the expression of miRNAs in whole islets as a function of glucose levels. There are three levels and one replicate for each condition. The third exeriment is a comparison of whole islets taken from human donors that were suspected/confirmed Type 2 diabetic or considered controls. There are 3 controls and 4 T2D samples.
2013-12-01 | E-GEOD-52314 | biostudies-arrayexpress
Project description:Little is known about the contribution of the epigenome to the pathophysiology of type 2 diabetes (T2D). Here we have used genome-wide DNA methylation profiling to obtain the first comprehensive DNA methylation data set for human T2D pancreatic islets. Therefore, we analyzed the methylation profile of 27,578 CpG sites affiliated to more than 14,000 genes in 16 samples of pancreatic islets, 11 normal and 5 type 2-diabetic. Keywords: DNA methylation Keywords: Methylation profiling by array We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA BeadChip array) in genomic DNA obtained from pnacreatic islets of 11 non-diabetic and 5 type-2-diabetic male human donors to identify genes that are differentially methylated in T2D.
2012-04-22 | E-GEOD-21232 | biostudies-arrayexpress
Project description:We employed a microarray as a discovery platform to identify the differential gene expressions between hND islets and hT2DM islets. 4805 genes with differential expression (fold change >2) were manifested in hT2DM islets. Inflammatory response and immune response were the mostly upregulated biological processes distinguished betwee hND islets and T2DM islets. Results provided insight into the molecular mechanisms in T2DM.
2021-08-03 | GSE118139 | GEO
Project description:Type 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo.
2013-12-01 | GSE52314 | GEO
Project description:We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples. Human islets were isolated from the pancreas of organ donors by collagenase digestion followed by density gradient purification, then hand-picked and cultured 2 days in M199 culture medium.
2010-12-01 | E-GEOD-25724 | biostudies-arrayexpress
Project description:Diabetes mellitus (DM) is a leading cause of chronic kidney disease and the pathobiology of diabetic nephropathy is widely studied. Less, however, is known about urinary bladder disease in DM despite dysfunctional voiding being a common clinical problem. We hypothesised that diabetic cystopathy would have a characteristic molecular signature, due to the adaptive response to increased urine load combined with the metabolic impacts of DM. To distinguish the consequences of DM from polyuria we compared bladders of untreated control, diabetic (streptozotocin-induced) and sucrose-treated male Wistar rats after 16 weeks using gene array
2021-07-17 | E-MTAB-9255 | biostudies-arrayexpress
Project description:Results Platelets in non-diabetic patients demonstrated miRNA expression profiles comparable to previously published data. The miRNA expression profiles of platelets in diabetics were similar. Statistical analysis unveiled only three miRNAs (miR-377-5p, miR-628-3p, miR-3137) with high reselection probabilities in resampling techniques, corresponding to signatures with only modest discriminatory performance. Functional annotation of predicted targets for these miRNAs pointed towards an influence of diabetes mellitus on mRNA processing. Conclusions/interpretation We did not find any major differences in platelet miRNA profiles between diabetics and non-diabetics. Minor differences pertained to miRNAs associated with mRNA processing. Thus, previously described differences in plasma miRNAs between diabetic and nondiabetic patients cannot be explained by plain changes in the platelet miRNA profile. Platelet miRNA profiles were assessed in clinically stable diabetic and nondiabetic patients (each n=30). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA profiling was performed using LNA micro-array technology (miRBase 18.0, containing 1,917 human miRNAs). Effects of diabetes mellitus were explored by univariate statistical tests for each miRNA, adjusted for potential confounders, and by developing a multivariable signature, which was evaluated by resampling techniques. Platelet phenotype was assessed by light transmission aggregometry and impedance aggregometry.
2014-03-14 | E-GEOD-44093 | biostudies-arrayexpress
Project description:We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples.
2010-12-01 | GSE25724 | GEO