Research in the mouse indicates that all three pancreas epithelial compartments derive from a single and transient progenitor. Now, a study of the human fetal pancreas identifies a leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cell population capable of generating all exocrine and endocrine pancreatic lineages.

Andersson-Rolf et al. derived pancreas organoid lines from gestational weeks 8–17 human pancreatic samples. They observed that lines derived from 15–16-gestational-week samples could generate all three pancreatic lineages, namely acinar-, ductal- and endocrine-lineage cells, as well as expand in culture for over two years. Further experiments, including single-cell transcriptomics, RNA velocity and reporter organoid analyses, identified a population of LGR5+ cells in human fetal pancreas tissue and in the organoids. Finally, the researchers showed that pancreatic organoids derived from single LGR5+ cells were capable of long-term expansion in vitro and generating the three pancreas epithelial cell lineages, as shown also with transplantation of the organoids into mice.