Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing.

A chronic inability to maintain blood glucose homeostasis leads to diabetes, which can damage multiple organs. The pancreatic islets regulate blood glucose levels through the coordinated action of islet cell-secreted hormones, with the insulin released by ß-cells playing a crucial role in this process. Diabetes is caused by insufficient insulin secretion due to ß-cell loss, or a pancreatic dysfunction. The restoration of a functional ß-cell mass might, therefore, offer a cure. To this end, major efforts are underway to generate human ß-cells de novo, in vitro, or in vivo. The efficient generation of functional ß-cells requires a comprehensive knowledge of pancreas development, including the mechanisms driving cell fate decisions or endocrine cell maturation. Rapid progress in single-cell RNA sequencing (scRNA-Seq) technologies has brought a new dimension to pancreas development research. These methods can capture the transcriptomes of thousands of individual cells, including rare cell types, subtypes, and transient states. With such massive datasets, it is possible to infer the developmental trajectories of cell transitions and gene regulatory pathways. Here, we summarize recent advances in our understanding of endocrine pancreas development and function from scRNA-Seq studies on developing and adult pancreas and human endocrine differentiation models. We also discuss recent scRNA-Seq findings for the pathological pancreas in diabetes, and their implications for better treatment.