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No evidence for β cell neogenesis in murine adult pancreas.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2013 May; Vol. 123 (5), pp. 2207-17. Date of Electronic Publication: 2013 Apr 24. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors metabolism
Cell Proliferation
Cell Separation
Female
Flow Cytometry
Green Fluorescent Proteins metabolism
Immunohistochemistry
Inflammation
Insulin genetics
Insulin metabolism
Mice
Mice, Transgenic
Microscopy, Fluorescence
Nerve Tissue Proteins metabolism
RNA metabolism
Time Factors
Insulin-Secreting Cells cytology
Pancreas cytology
Pancreas metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 123
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 23619362
- Full Text :
- https://doi.org/10.1172/JCI66323