Single-cell chromatin landscapes of human islets in normoglycemia, prediabetes and type 2 diabetes

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. characterization of gene regulatory programs in individual islet cell types under both homeostatic and diabetic conditions.

本研究采用单细胞核ATAC测序（single cell nucleus ATAC-seq，snATAC-seq）对34名供体的218973个胰岛细胞进行测序分析，供体涵盖非糖尿病、糖尿病前期及2型糖尿病（type 2 diabetic, T2D）患者。本研究解析了胰岛细胞亚型在2型糖尿病进展过程中的调控程序变化，阐明了上述调控程序与2型糖尿病遗传易感风险的关联，并通过等位基因不平衡定位分析，明确了候选2型糖尿病致病变异的细胞亚型特异性功能，同时完成了稳态及糖尿病状态下单个胰岛细胞亚型的基因调控程序表征。