Progenitor cell niches in the duodenum and pancreatic duct system and pancreatic endocrine fate commitment

Th e liver, biliary tree and pancreas derive embryologically from a common precursor in the primitive duodenum. Niches of endoderm progenitors remain in specific anatomical locations in adult organs. Our aim was to study the phenotype of progenitor cell niches in duodenum and bilio-pancreatic system, and their pancreatic endocrine differentiation potency. Human organs from control (n=5) or type 2 diabetes mellitus (T2DM: n=5) subjects were studied. In vitro, progenitor cells were isolated from human duodenum and cultured in a well-defi ned pancreatic differentiation medium (PDM). In mice (n=10), pancreatic islets were damaged by streptozotocin (STZ) injection. Samples were examined by immunohistochemistry, immunofluorescence and RT-qPCR. In normal organs, cells with a progenitor-like phenotype were present in duodenal submucosal glands (dSG), pancreatic duct glands (PDG), and peribiliary glands (PBG). Insulin+ cells were rarely found in PDGs and PBGs, but not in dSGs. In T2DM, the β-cell loss was associated with a higher proportion of central islets, an increased proliferation of PDGs, and the appearance of pancreatic islet-like structures within pancreatic duct walls. Moreover, insulin+ cells appeared within PBGs and, rarely, in dSGs. Isolated dSG cells from normal human duodena showed in vitro capability to commit toward endocrine pancreatic fate when cultured in PDM. STZ mice were characterized by an overall reduced islet area, by an increased proportion of central islets, and by modifications in PDG and dSG cell compartment. Progenitor cells in adult bilio-pancreatic duct system and in dSG glands have the capability to commit towards an endocrine pancreatic fate. Our findings could contribute to defining the role of progenitor cell compartments in islet regeneration.