No evidence for β cell neogenesis in murine adult pancreas

J Clin Invest. 2013 May;123(5):2207-17. doi: 10.1172/JCI66323. Epub 2013 Apr 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Insulin-Secreting Cells / cytology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Nerve Tissue Proteins / metabolism
  • Pancreas / cytology*
  • Pancreas / metabolism*
  • RNA / metabolism
  • Time Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • Insulin
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Green Fluorescent Proteins
  • RNA