title: No evidence for β cell neogenesis in murine adult pancreas.
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.
authors.affiliation: Division of Pediatric Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.forename: Zean
authors.initials: Z
authors.lastname: Chen
authors.forename: Chiyo
authors.initials: C
authors.lastname: Shiota
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.forename: Ping
authors.initials: P
authors.lastname: Guo
authors.forename: Yousef
authors.initials: Y
authors.lastname: El-Gohary
authors.forename: Jose
authors.initials: J
authors.lastname: Paredes
authors.forename: Carey
authors.initials: C
authors.lastname: Welsh
authors.forename: John
authors.initials: J
authors.lastname: Wiersch
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D012313:RNA; C407737:Neurog3 protein, mouse