First Author | Xiao X | Year | 2013 |
Journal | J Clin Invest | Volume | 123 |
Issue | 5 | Pages | 2207-17 |
PubMed ID | 23619362 | Mgi Jnum | J:264457 |
Mgi Id | MGI:6196984 | Doi | 10.1172/JCI66323 |
Citation | Xiao X, et al. (2013) No evidence for beta cell neogenesis in murine adult pancreas. J Clin Invest 123(5):2207-17 |
abstractText | Whether facultative beta cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track beta 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 beta cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that beta cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of beta cell loss, beta cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting beta 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 beta cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions. |