Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12288300_1.fastq.gz | Fastqsanger.gz | |||
| SRR12288300_2.fastq.gz | Fastqsanger.gz | |||
| SRR12288301_1.fastq.gz | Fastqsanger.gz | |||
| SRR12288301_2.fastq.gz | Fastqsanger.gz | |||
| SRR12288302_1.fastq.gz | Fastqsanger.gz |
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Project description:The global prevalence of type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal T2D on metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal T2D increases the susceptibility to diabetes in offspring through the gametic epigenetic alterations. Paternal T2D led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of T2D fathers exhibited altered gene expression patterns in the pancreatic islets, with downregulation of several genes involved in glucose metabolism and insulin signaling pathway. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal T2D, including reproducible changes in methylation over several insulin signaling genes. Paternal T2D altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapped with that of pancreatic islets in offspring. Our study revealed, for the first time, that T2D can be inherited transgenerationally through the mammalian germline by an epigenetic manner. Examination of the effect of paternal T2D on the DNA methylation in the pancreatic islets of offspring and in the sperm of father.
2013-01-02 | E-GEOD-43238 | biostudies-arrayexpress
Project description:Type 2 diabetes (T2D), one of the most common metabolic diseases, is the result of insulin resistance or impaired insulin secretion by mitochondrial dysfunctions. Mitochondrial DNA (mtDNA) polymorphisms play an important role in physiological and pathological characteristics of T2D, however, their mechanism is poorly understood. To directly identify candidate mtDNA variants associated with T2D at the genome-wide level, we constructed forty libraries from ten patients with T2D and thirty control individuals for deep sequencing. We characterized their mtDNA atlas, and analyzed their single nucleotide polymorphisms (MtSNPs), insertions and deletions (InDels), and screened potential mtDNA mutation sites associated with T2D. We found ten mtDNA polymorphisms at nucleotides 489T > C, 3105AC > A, 3107N > C, 8701A > G, 9540T > C, 10398A > G, 10400C > T, 10873T > C, 12705C > T and 14783T > C that showed a significant difference between patients and control subjects. Therefore, our results characterize mtDNA atlas of patients with T2D, and further demonstrate that mtDNA variants are participated in the pathophysiology of T2D and other diseases. In addition, mtDNA variants may be candidate molecular biomarkers of T2D, and they may be valuable for early diagnosis of T2D in the future.
2022-08-30 | GSE136892 | GEO
Project description:In this study, we used single cell nucleus ATAC-seq (snATAC-seq) to profile 218,973 islet cells from 34 individuals, including islets from non-diabetic, pre-diabetic and type 2 diectic (T2D) donors. We characterize changes in regulatory programs of islet cell types in T2D progression, describe the relationship of these programs to genetic risk for T2D, and use allelic imbalance mapping to define cell type-specific functions for candidate T2D causal variants.
2023-02-07 | GSE169453 | 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:Dysregulation in expression of microRNAs (miRNAs) in various tissues has been linked to a wide spectrum of diseases, including Type 2 Diabetes mellitus (T2D). In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients with tissues from T2D rat models. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Using luciferase assay, we further demonstrated that miR-144 directly targets IRS1 and showed its effects on protein expression via immunocytochemistry. From this cross-sectional study in humans, we have identified signature miRNAs which could explain the pathogenesis of T2D. Whether miRNAs like miR-144 could be potential therapeutic targets for management of T2D will need to be explored by further mechanistic and functional studies.
2010-12-18 | GSE26167 | GEO
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:The functional heterogeneity of β-cells is important for metabolism and diseases, but the nature and mechanism of such variation at molecular level remain elusive. Here we explore this question by comparing both single cell RNA-seq and single cell ATAC-seq maps of healthy and type II diabetic (T2D) human islets. We dissect the T2D-associated single cell trajectory and identified signature genes and enhancers in β-cells. We also map the 3D genome of both α- and β-cells with low-input eHi-C approach to unravel the cell type-specific gene regulatory circuits. Strikingly, more than one third of the T2D signature genes show significant intra-donor heterogeneity at single cell level; these genes are functionally distinct from other signature genes that are largely invariant among cells from the same individual but differentially expressed between donors, suggesting different roles in T2D pathogenesis. Importantly, we identified consistent intra-donor variations at both transcriptomic and epigenomic levels, which strongly support the heterogenous β-cell states and transcription programs. Finally, we construct the disease-signature regulatory networks and pinpointed HNF1A as one of the top transcription factors governing T2D-associated β-cell heterogeneity. Taken together, we provide the first multi-omic characterization of β-cell heterogeneity and reveals its connection to T2D.
2023-08-09 | GSE195522 | GEO