title: Neurogenin3 activation is not sufficient to direct duct-to-beta cell transdifferentiation in the adult pancreas.
abstract: It remains controversial whether adult pancreatic ducts harbor facultative beta cell progenitors. Because neurogenin3 (Ngn3) is a key determinant of pancreatic endocrine cell neogenesis during embryogenesis, many studies have also relied upon Ngn3 expression as evidence of beta cell neogenesis in adults. Recently, however, Ngn3 as a marker of adult beta cell neogenesis has been called into question by reports of Ngn3 expression in fully-developed beta cells. Nevertheless, direct evidence as to whether Ngn3 activation in adult pancreatic duct cells may lead to duct-to-beta cell transdifferentiation is lacking. Here we studied two models of Ngn3 activation in adult pancreatic duct cells (low-dose alloxan treatment and pancreatic duct ligation) and lineage-traced Ngn3-activated duct cells by labeling them through intraductal infusion with a cell-tagging dye, CFDA-SE No dye-labeled beta cells were found during the follow-up in either model, suggesting that activation of Ngn3 in duct cells is not sufficient to direct their transdifferentiation into beta cells. Therefore, Ngn3 activation in duct cells is not a signature for adult beta cell neogenesis.
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224. Electronic address: xiangwei.xiao@chp.edu.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Ping
authors.initials: P
authors.lastname: Guo
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Chiyo
authors.initials: C
authors.lastname: Shiota
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Yousef
authors.initials: Y
authors.lastname: El-Gohary
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: John
authors.initials: J
authors.lastname: Wiersch
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Iljana
authors.initials: I
authors.lastname: Gaffar
authors.affiliation: From the Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224. Electronic address: gittesgk@upmc.edu.
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D054338:Cell Transdifferentiation / Q000502:physiology*; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D013388:Succinimides; C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; C407737:Neurog3 protein, mouse
keywords: Beta Cell; Flow Cytometry; Pancreas; Reprogramming; Transcription