Understanding development and cellular plasticity in the pancreas in health and disease

Pancreatic development is a dynamic process shaped by coordinated interactions between surrounding non-pancreatic tissues and intrinsic transcription factors, integrated through gene regulatory networks. Advances in single-cell genomics and lineage-tracing technologies have substantially expanded our understanding of pancreatic biology, elucidating the ontogeny of pancreatic cells, their diversity and the intercellular interactions that govern them. In this Review, we examine the emergence of pancreatic cell lineages in the embryo through the lens of cellular plasticity, emphasizing how reciprocal interactions with the microenvironment influence lineage decisions. We also draw parallels between developmental and pathological processes, highlighting the dual role of plasticity: enabling lineage specification during development and supporting regenerative responses upon injury or in disease states. A deeper appreciation of the mechanisms underlying pancreatic cell identity and plasticity holds the potential to inform the development of new therapeutic modalities for pancreatic diseases, such as diabetes and pancreatic cancer.