No evidence for β cell neogenesis in murine adult pancreas
Open Access
- 24 April 2013
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 123 (5), 2207-2217
- https://doi.org/10.1172/jci66323
Abstract
Whether facultative β cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track β cell neogenesis in vivo, we generated transgenic mice that transiently coexpress mTomato and GFP in a time-sensitive, nonconditional Cre-mediated manner, so that insulin-producing cells express GFP under control of the insulin promoter, while all other cells express mTomato (INSCremTmG mice). Newly differentiated β cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that β cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of β cell loss, β cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting β cells in the ligated pancreatic tail after pancreatic ductal ligation. These results are consistent with some recent reports, but argue against the widely held belief that NGN3 marks cells undergoing endocrine neogenesis in the pancreas. Our data suggest that β cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions.Keywords
This publication has 54 references indexed in Scilit:
- Conversion of adult pancreatic α-cells to β-cells after extreme β-cell lossNature, 2010
- Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and functionProceedings of the National Academy of Sciences of the United States of America, 2009
- Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birthProceedings of the National Academy of Sciences of the United States of America, 2008
- Generation and Regeneration of Cells of the Liver and PancreasScience, 2008
- On the origin of the β cellGenes & Development, 2008
- Recovery from diabetes in mice by β cell regenerationJCI Insight, 2007
- Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regenerationJCI Insight, 2007
- Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACSProceedings of the National Academy of Sciences of the United States of America, 2007
- Pancreatic organogenesis — developmental mechanisms and implications for therapyNature Reviews Genetics, 2002
- Dual Roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic β Cell-specific Gene Knock-outs Using Cre RecombinasePublished by Elsevier BV ,1999