Origin of pancreatic endocrine cells from biliary duct epithelium
- 22 September 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 65 (21), 3467-3480
- https://doi.org/10.1007/s00018-008-8427-1
Abstract
We describe an explant culture system to study the formation of pancreatic-type endocrine cells by the biliary tract. In this model, β-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, β-cells in cultures isolated from Alb-Cre-R26R-LacZ mice are β-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 β-cells formed, while EGF+LIF completely inhibits their formation.Keywords
This publication has 21 references indexed in Scilit:
- SOX9 is required for maintenance of the pancreatic progenitor cell poolProceedings of the National Academy of Sciences of the United States of America, 2007
- β cells occur naturally in extrahepatic bile ducts of miceJournal of Cell Science, 2007
- Ectopic pancreas formation in Hes1-knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreasJCI Insight, 2006
- Current status of pancreatic islet transplantationClinical Science, 2006
- Gene therapy for diabetes: reinventing the isletTrends in Endocrinology & Metabolism, 2006
- Loss of the Major Duodenal Papilla Results in Brown Pigment Biliary Stone Formation in Pdx1 Null MiceGastroenterology, 2006
- Pancreatic differentiationJournal of Hepato-Biliary-Pancreatic Surgery, 2005
- Gene regulatory factors in pancreatic developmentDevelopmental Dynamics, 2003
- Functional, Persistent, and Extended Liver to Pancreas TransdifferentiationPublished by Elsevier BV ,2003
- Induction of Pancreatic Differentiation by Signals from Blood VesselsScience, 2001