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

Abstract

Pancreatic islets are comprised 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 non-diabetic, type 1 diabetes autoantibody positive, type 1 diabetic, and type 2 diabetic donors from the Human Pancreas Analysis Program. We identified 10 distinct cell types, annotated sub-populations of several cell types, and defined cell typespecific 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 beta cells from donors with type 1 diabetes. To facilitate user interaction, we provide several single cell visualization and reference mapping tools, as well as open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology.