Title: Patch-Seq Links Single-Cell Transcriptomes to Human Islet Dysfunction in Diabetes

Author: Joan Camunas-Soler, Xiao-Qing Dai, Yan Hang, Austin Bautista, James Lyon, Kunimasa Suzuki, Seung K. Kim, Stephen R. Quake, Patrick E. MacDonald

IssueVolume:

Abstract: Impaired function of pancreatic islet cells is a major cause of metabolic dysregulationand disease in humans. Despite this, it remains challenging to directly link physiologicaldysfunction in islet cells to precise changes in gene expression. Here we show thatsingle-cell RNA sequencing combined with electrophysiological measurements of exocytosisand channel activity (patch-seq) can be used to link endocrine physiology and transcriptomesat the single-cell level. We collected 1,369 patch-seq cells from the pancreata of34 human donors with and without diabetes. An analysis of function and gene expression networksidentified a gene set associated with functional heterogeneity in cells that canbe used to predict electrophysiology. We also report transcriptional programs underlyingdysfunction in type 2 diabetes and extend this approach to cryopreserved cells fromdonors with type 1 diabetes, generating a valuable resource for understanding isletcell heterogeneity in health and disease.

DOI: 10.1016/j.cmet.2020.04.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30187-X