Origin of pancreatic endocrine cells from biliary duct epithelium

Abstract

We describe an explant culture system to study the formation of pancreatic-type endocrine cells by the biliary tract. In this model, beta-cells and other endocrine cells appear in the biliary duct epithelium and their number increases. Evidence for an origin from the duct epithelium is threefold. Firstly, differentiating cells transiently co-express insulin and bind Dolichos lectin. Secondly, beta-cells in cultures isolated from Alb-Cre-R26R-LacZ mice are beta-galactosidase positive. Thirdly, co-culture of biliary epithelium and ROSA26 pancreatic buds shows that endocrine cells do not migrate from the pancreas. The expression of the pancreatic transcription factors Pdx1, HNF6 and Sox9 is widespread, as is Hes1, which represses endocrine development, while that of Ngn3, which is a proendocrine transcription factor, is transient, consistent with an early stage of endocrine cell differentiation. Nicotinamide will increase the number of beta-cells formed, while EGF+LIF completely inhibits their formation.

In vivo reprogramming of Sox9 + cells in the liver to insulin-secreting ducts

“…In the normal extrahepatic biliary system (24,25) and in certain pathologies involving β-cell neogenesis (26,27), it is possible to find pancreatic endocrine cells budding off ducts, but in our case it is the actual cells of the ducts themselves that are producing the hormones. We have also shown that multihormone-producing cells can exhibit glucose-sensitive insulin secretion.…”

The Comparative Anatomy of Islets

“…2 and 3). Scattered insulin cells are also found associated with the bile duct as is also found in higher vertebrates (Eberhard et al 2008). No glucagon, PP, or ghrelin (Heller and Christensen 2009) cells have been identified in the structure Fig.…”

Cellular Plasticity within the Pancreas— Lessons Learned from Development

“…A possible explanation for this could be the existence of a pancreatic ‘‘stemlike’’ cell capable of giving rise to hepatocytes and originating from duct-like structures. Alternatively, the origin of these cells might lie within the biliary tree, which is known to harbor cells that can contribute to the endocrine lineage (Dutton et al, 2007; Eberhard et al, 2008). The biliary epithelium possesses the ability to form endocrine cells in the absence of Hes-1 , which represses Ngn-3 expression (Sumazaki et al, 2004).…”