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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195523 | GEO | 2023/08/09

REPOSITORIES: GEO

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

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.

2023-08-10 | GSE234754 | GEO

Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scRNASeq)

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scATACSeq)

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets (Hi-C)

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

Project description:Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scATACSeq)

Project description:Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scATACSeq)

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scRNASeq)

Project description:Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scRNASeq)

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Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets (Hi-C)

Project description:Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets (Hi-C)

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Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes.

Project description:Type 1 diabetes (T1D) is an autoimmune disease in which immune cells destroy insulin-producing beta cells. The aetiology of this complex disease is dependent on the interplay of multiple heterogeneous cell types in the pancreatic environment. Here, we provide a single-cell atlas of pancreatic islets of 24 T1D, autoantibody-positive and nondiabetic organ donors across multiple quantitative modalities including ~80,000 cells using single-cell transcriptomics, ~7,000,000 cells using cytometry by time of flight and ~1,000,000 cells using in situ imaging mass cytometry. We develop an advanced integrative analytical strategy to assess pancreatic islets and identify canonical cell types. We show that a subset of exocrine ductal cells acquires a signature of tolerogenic dendritic cells in an apparent attempt at immune suppression in T1D donors. Our multimodal analyses delineate cell types and processes that may contribute to T1D immunopathogenesis and provide an integrative procedure for exploration and discovery of human pancreatic function.

| S-EPMC8938904 | biostudies-literature

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