Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic

Abstract

Summary: Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1β and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1β and SOX9. Only the CD24high (Hnfβ high/Sox9 high) subpopulation was able to form organoids. : In this article, Bonner-Weir and colleagues show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after replication. Using cell surface markers, they isolated living subpopulations of duct cells with different expression profiles and potential to form organoids. Keywords: heterogeneity, organoid, pancreatic ductal cells