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Whole-islet RNA-sequencing analysis of human pancreas and type 2 diabetes.

ABSTRACT: Whole-islet RNA-sequencing analysis of human pancreas and type 2 diabetes.

PROVIDER: PRJEB15398 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR1629982_1.fastq.gz	Fastqsanger.gz
	ERR1629982_2.fastq.gz	Fastqsanger.gz
	ERR1629983_1.fastq.gz	Fastqsanger.gz
	ERR1629983_2.fastq.gz	Fastqsanger.gz
	ERR1629984_1.fastq.gz	Fastqsanger.gz

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Whole-islet RNA-sequencing analysis of human pancreas from healthy individuals and type 2 diabetes patients

Project description:We performed whole-islet RNA-sequencing of human pancreatic islets from healthy and T2D individuals in order to compare the expression data to the corresponding single-cell RNA-sequencing data from the same donors (related single-cell study: Single-cell analysis of human pancreas and T2D, deposited at ArrayExpress under accession E-MTAB-5061: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5061/).

2016-09-22 | E-MTAB-5060 | biostudies-arrayexpress

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Project description:<h4><strong>AIMS/HYPOTHESIS: </strong>Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.</h4><h4><strong>METHODS: </strong>We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.</h4><h4><strong>RESULTS: </strong>In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.</h4><h4><strong>CONCLUSIONS/INTERPRETATION: </strong>Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.</h4>

2022-01-19 | MTBLS802 | MetaboLights

Type 2 Diabetes Specific Spatial Differential Gene Expression in Pancreas Visium Data

Project description:Understanding the spatial distribution of gene expression in the pancreas could provide new insights into its function and islet biology. Visium spatial gene expression is a powerful tool for quantifying gene expression of cells within their spatial context. We describe the generation and analysis of spatial transcriptomics data from six pancreas samples from healthy donors. Our analysis revealed high expression of INS within islets. However, we also identified a bleed of highly abundant islet genes (e.g., INS, GCG) into surrounding tissue areas. Through computational analyses, we successfully corrected for this bleed. We then identify genes which are spatially differentially expressed in the Type 2 Diabetes samples. We provide these data for researchers to study the organization of the pancreas and islets.

2024-08-31 | GSE264331 | GEO

Whole population RNASeq of pancreatic islet macrophages during autoimmune diabetes progression

Project description:Whole population RNASeq of pancreatic islet macrophages during autoimmune diabetes progression.

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Pancreatic islet, pancreas and gallbladder from human and mouse

Project description:Collection of pancreatic islet, pancreas and gallbladder from human and mouse whole transcriptome data.

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Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

Project description:Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

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Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

Project description:Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac b-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.

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Project description:Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. We analysed gene expression by RNA-seq in four types of immune cells from five genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’) and in five at-risk children matched for sex, age and HLA who had not progressed to diabetes (‘non-progressors’).

2022-03-09 | GSE185190 | GEO

RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes

Project description:Pancreatic islet cells are critical for maintaining normal blood glucose levels and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic α-, β-, δ- and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell type specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human α- and β-cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community.

2016-08-31 | GSE81608 | GEO

ARID1A loss in pancreas leads to islet developmental defect and metabolic disturbance ,Islet cell ChIP-Seq HDAC6 arid1a

Project description:ARID1A is a tumor suppressor gene mutated in 7-10% of pancreatic cancer patients. However, its function in pancreas development and endocrine regulation is unclear. We generated mice that lack Arid1a expression in the pancreas. Our results showed that deletion of the Arid1a gene in mice caused a reduction in islet numbers and insulin production, both of which are associated with diabetes mellitus (DM) phenotype.we performed chromatin immunoprecipitation-sequencing analysis (ChIP-seq) to study genome-wide HDAC6 occupancy in the control and Arid1a-depleted islet cells.

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