Expression data from human pancreatic islets
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38642 | GEO | 2012/07/05
SECONDARY ACCESSION(S): PRJNA168302
REPOSITORIES: GEO
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Project description:Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Islets from cadaver donors (54 non-diabetic and 9 diabetic) were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.
2012-07-05 | E-GEOD-38642 | 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 have studied the impact of T2D on open chromatin in human pancreatic islets. We used assay for transposase-accessible chromatin using sequencing (ATAC-seq) to profile open chromatin in islets from T2D and non-diabetic donors. We identified ATAC-seq peaks representing open chromatin regions in islets of non-diabetic and diabetic donors. The majority of ATAC-seq peaks mapped near transcription start sites. Additionally, peaks were enriched in enhancer regions and in regions where islet-specific TFs bind. Islet ATAC-seq peaks overlap with SNPs associated with T2D and with additional SNPs in LD with known T2D SNPs. There was enrichment of open chromatin regions near highly expressed genes in human islets.
2019-04-06 | GSE129383 | GEO
Project 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). Islets from cadaver donors were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.
2014-07-17 | E-GEOD-50397 | biostudies-arrayexpress
Project description:Pancreatic islet beta cell heterogeneity has been identified, which plays a pivotal role in the pathological alterations of pancreatic islets in type 2 diabetes (T2D) mice. However, pathological alterations of beta cells in type 2 diabetes (T2D) mice remain to be investigated. We isolated pancreatic islets from the control and T2D mice and conducted scRNA-seq analysis using the 10x Genomics platform. Pathological alterations of beta cells in T2D were also explored.
2022-04-09 | GSE200531 | GEO
Project description:Genetic studies have identified ≥240 loci associated with type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating gene expression in pancreatic islets have provided key insights into the molecular drivers of T2D pathophysiology through comprehensive genetic and genomic analyses. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present the largest genetic and genomic analysis of miRNA expression in human islets to date, spanning 63 participants. We characterize the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into cis- and trans- genetic components and mapping cis loci associated with miRNA expression (miRNA-eQTLs). We find (a) 81 heritable miRNAs, which we show are primarily regulated by trans-acting genetic effects, and (b) 5 miRNA-eQTLs. To evaluate the impact of miRNA expression on T2D, we use several different strategies to nominate T2D-associated miRNAs. First, we colocalize miRNA-eQTLs with genetic studies of T2D and several T2D-related traits and identify one miRNA, miR-1908, that shares genetic signals for blood glucose and HbA1c. Next, we intersect miRNA seed regions with credible set SNPs from T2D and T2D-related genetic studies and find 46 miRNAs that may have altered binding and function due to disrupted seed regions. Finally, we perform differential expression analysis and identify 38 miRNAs associated with either T2D status, body mass index, sex, or a polygenic score for HbA1c levels. To validate identified miRNAs, we perform chromatin run-on sequencing and confirm differential transcription of T2D-associated miRNAs.
2023-01-29 | GSE196797 | GEO
Project description:Pancreatic islet (dys)function is central to glucose homeostasis and type 2 diabetes (patho)physiology. Human islets consist of multiple endocrine (alpha, beta, delta, gamma), endothelial, and resident/inflitrating immune cells whose coordinated functions modulate glucose mobilization or disposal. Single cell transcriptome profiling (scRNA-seq) studies have been applied to dissect human islet cellular heterogeneity, identify islet cell (sub)populations, and define their molecular repertoire. However, precise understanding of cell type-specific alterations in type 2 diabetic vs. non-diabetic individuals is lacking, due in part to the limited number of individuals or single cell transcriptomes per individual profiled for comparison. Here, we create a comprehensive single cell transcriptome atlas of 245,878 human islet cells from 48 individuals spanning non-diabetic (ND), pre-diabetic (PD), and type 2 diabetic (T2D) states and matched for sex, age, and ancestry and define marker gene sets that are robustly expressed across disease states for each of the 14 cell types identified. We observe significant decreases in the number of beta cells sampled from T2D vs. ND or PD donors. Two of eight putative beta cell subpopulations, with ‘high functioning’ and ‘senescent’ cell gene signatures, increase and decrease in T2D donor islets, respectively. Importantly, we identify 511 differentially expressed genes in beta cells from T2D vs. ND donors. This includes monogenic and type 2 diabetes effector genes, such as HNF1A, DGKB, ST6GAL1, and FXYD2, for which genetic and environmental effects on their expression is concordant. Human beta cell and islet knockdown of selected newly-identified down-regulated genes impairs beta cell viability or function. Together, this study provides new and robust, cell type-resolved insights on the cellular and molecular changes in healthy vs. diabetic human islets and represents a valuable resource to the islet biology and type 2 diabetes communities.
2023-03-30 | GSE221156 | GEO
Project description:Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA profile of human pancreatic islets and of enriched beta-cell populations, and to explore their potential involvement in T2D susceptibility. We used Illumina small RNA sequencing to profile the miRNA fraction in three preparations each of primary human islets and of enriched beta-cells generated by fluorescence-activated cell sorting. In total, 366 miRNAs were found to be expressed (i.e. >100 cumulative reads) in islets and 346 in beta-cells; of the total of 384 unique miRNAs, 328 were shared. A comparison of the islet-cell miRNA profile with those of 15 other human tissues identified 40 miRNAs predominantly expressed (i.e. >50% of all reads seen across the tissues) in islets. Several highly-expressed islet miRNAs, such as miR-375, have established roles in the regulation of islet function, but others (e.g. miR-27b-3p, miR-192-5p) have not previously been described in the context of islet biology. As a first step towards exploring the role of islet-expressed miRNAs and their predicted mRNA targets in T2D pathogenesis, we looked at published T2D association signals across these sites. We found evidence that predicted mRNA targets of islet-expressed miRNAs were globally enriched for signals of T2D association (p-values <0.01, q-values <0.1). At six loci with genome-wide evidence for T2D association (AP3S2, KCNK16, NOTCH2, SCL30A8, VPS26A, and WFS1) predicted mRNA target sites for islet-expressed miRNAs overlapped potentially causal variants. In conclusion, we have described the miRNA profile of human islets and beta-cells and provide evidence linking islet miRNAs to T2D pathogenesis. Examination of the miRNA profiles in 3 preparations of isolated pancreatic islets and 3 preparations of FACS-enriched pancreatic beta-cells
2013-06-07 | E-GEOD-47720 | biostudies-arrayexpress
Project description:Global microRNA (miRNA) profiling was performed in 18 human islet donors using Exiqon’s LNA (locked nucleic acid)-based array platform. Donors were divided into three groups according to their HbA1c levels and type-2 diabetes diagnosis (normal glucose tolerance - NGT, impaired glucose tolerance - IGT, diagnosed with type-2 diabetes-T2D). To identify miRNAs with altered expression due to glyceamic status, donors were matched for age, gender and BMI and differential expression analysis was performed in 7 NGT vs 7 IGT/T2D donors using Significance Analysis of Microarrays (SAM) based on False Discovery Rate (FDR) statistics.
2022-02-28 | E-MTAB-11125 | biostudies-arrayexpress
Project 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 Islets from cadaver donors (57 non-diabetic and 20 diabetic) were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.
2012-10-23 | E-GEOD-41762 | biostudies-arrayexpress