Single-cell multiome (ATAC and RNA) landscapes of human islets in normoglycemia, prediabetes and type 2 diabetes. Single-cell multiome (ATAC and RNA) landscapes of human islets in normoglycemia, prediabetes and type 2 diabetes

We used single cell multiome (ATAC and RNA) sequencing to profile 85266 islet cells from 20 individuals, including islets from non-diabetic, pre-diabetic and type 2 diabetic (T2D) donors. We characterize changes in regulatory programs of islet cell types and subtypes 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. Overall design: characterization of gene regulatory programs in individual islet cell types under both homeostatic and diabetic conditions.

本研究采用单细胞多组学（ATAC与RNA）测序技术，对来自20名受试者的85266个胰岛细胞进行细胞图谱分析，受试者涵盖非糖尿病、糖尿病前期及2型糖尿病（T2D）供体的胰岛组织。本研究解析了胰岛细胞类型及亚型的调控程序在2型糖尿病进展过程中的动态变化，阐明了此类调控程序与2型糖尿病遗传易感风险的关联，并通过等位基因失衡图谱分析，明确了候选2型糖尿病致病变异的细胞类型特异性功能。整体实验设计：解析稳态与糖尿病两种状态下单种胰岛细胞类型的基因调控程序特征。