Spatially organized cellular communities shape functional tissue architecture in the pancreas

Abstract

Organ function depends on the precise spatial organization of cells across multiple scales, from individual units to cellular communities that form local niches and, ultimately, higher-order structures. Although cell identities are increasingly well defined, the spatial arrangement and interactions among diverse cell types remain poorly understood. Here, we combine single-cell and spatial transcriptomics to map pancreatic cell populations across space and time, from embryonic development to adult homeostasis in mice. Using these maps, we resolve spatial heterogeneity among pancreatic cell types and uncover epithelial-mesenchymal units as basic tissue niches, which we functionally characterize in both mouse and human models. We also demonstrate that the mesenchymal lineage diversifies into various specialized subtypes during development, but this complexity diminishes over time, ultimately converging into a few fibroblast subtypes in adulthood. Together, our findings reveal how different progenitor lineages codevelop and organize into structured communities that establish a functional pancreas, providing a framework to guide in vitro organogenesis and tissue engineering for pancreatic diseases.