Recapitulating and Deciphering Human Pancreas Development From Human Pluripotent Stem Cells in a Dish

Here, we review how human pluripotent stem cell models of pancreas development have emerged and became an important tool to study human development and disease. Initially developed toward the production of β cells for diabetes therapy, the protocols have been refined based on knowledge of pancreas development in model organisms. While the cells produced are closer and closer to the end goal of a functional β cell, these models have also been used to carry out functional experiments addressing gene function and expression as well as regulatory and epigenetic landscape changes during human pancreas development. They thereby complement model organisms and reports from human genetic variants predisposing to different forms of diabetes, as well as observations on human fetal tissue. In this review, we therefore compare these different sources of information and discuss how human stem cell models are evolving to inform us on pancreatic diseases and possible treatments.