An Integrated Map of Cell Type–Specific Gene Expression in Pancreatic Islets

Pancreatic islets consist of multiple cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in type 1 and type 2 diabetes. Numerous studies have assessed transcription across individual cell types using single-cell assays; however, there is no canonical reference of gene expression in islet cell types that is also easily accessible for researchers to query and use in bioinformatics pipelines. Here we present an integrated map of islet cell type–specific gene expression from 192,203 cells from single-cell RNA sequencing of 65 donors without diabetes, donors who were type 1 diabetes autoantibody positive, donors with type 1 diabetes, and donors with type 2 diabetes from the Human Pancreas Analysis Program. We identified 10 distinct cell types, annotated subpopulations of several cell types, and defined cell type–specific marker genes. We tested differential expression within each cell type across disease states and identified 1,701 genes with significant changes in expression, with most changes observed in β-cells from donors with type 1 diabetes. To facilitate user interaction, we provide several single-cell visualization and reference mapping tools, as well as the open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology. ARTICLE HIGHLIGHTS: No canonical reference exists for cell type–specific gene expression from single-cell RNA sequencing of pancreatic islets. We generated an integrated single-cell RNA sequencing map from healthy and diseased pancreatic islets and included user-friendly resources for visualizing and querying the data. Most significant changes in gene expression exist in β-cells from donors with type 1 diabetes. Our study provides a suite of tools and resources for the diabetes community to easily access cell type–specific gene expression analyses in pancreatic islets.