BACKGROUND & AIMS: The mammalian pancreas has a strong regenerative potential, but the origin of organ restoration is not clear, and it is not known to what degree such a process reflects pancreatic development. To define cell differentiation changes associated with pancreatic regeneration in adult mice, we compared regeneration following caerulein-induced pancreatitis to that of normal pancreatic development. METHODS: By performing comparative histology for adult and embryonic pancreatic markers in caerulein-treated and control pancreas, we addressed cellular proliferation and differentiation (amylase, DBA-agglutinin, insulin, glucagon, beta-catenin, E-cadherin, Pdx1, Nkx6.1, Notch1, Notch2, Jagged1, Jagged2, Hes1), hereby describing the kinetics of tissue restoration. RESULTS: We demonstrate that surviving pancreatic exocrine cells repress the terminal exocrine gene program and induce genes normally associated with undifferentiated pancreatic progenitor cells such as Pdx1, E-cadherin, beta-catenin, and Notch components, including Notch1 , Notch2 , and Jagged2 . Expression of the Notch target gene Hes1 provides evidence that Notch signaling is reactivated in dedifferentiated pancreatic cells. Although previous studies have suggested a process of acino-to-ductal transdifferentiation in pancreatic regeneration, we find no evidence to suggest that dedifferentiated cells acquire a ductal fate during this process. CONCLUSIONS: Pancreatic regeneration following chemically induced pancreatitis in the mouse occurs predominantly through acinar cell dedifferentiation, whereby a genetic program resembling embryonic pancreatic precursors is reinstated.
BACKGROUND & AIMS: The mammalian pancreas has a strong regenerative potential, but the origin of organ restoration is not clear, and it is not known to what degree such a process reflects pancreatic development. To define cell differentiation changes associated with pancreatic regeneration in adult mice, we compared regeneration following caerulein-induced pancreatitis to that of normal pancreatic development. METHODS: By performing comparative histology for adult and embryonic pancreatic markers in caerulein-treated and control pancreas, we addressed cellular proliferation and differentiation (amylase, DBA-agglutinin, insulin, glucagon, beta-catenin, E-cadherin, Pdx1, Nkx6.1, Notch1, Notch2, Jagged1, Jagged2, Hes1), hereby describing the kinetics of tissue restoration. RESULTS: We demonstrate that surviving pancreatic exocrine cells repress the terminal exocrine gene program and induce genes normally associated with undifferentiated pancreatic progenitor cells such as Pdx1, E-cadherin, beta-catenin, and Notch components, including Notch1 , Notch2 , and Jagged2 . Expression of the Notch target gene Hes1 provides evidence that Notch signaling is reactivated in dedifferentiated pancreatic cells. Although previous studies have suggested a process of acino-to-ductal transdifferentiation in pancreatic regeneration, we find no evidence to suggest that dedifferentiated cells acquire a ductal fate during this process. CONCLUSIONS: Pancreatic regeneration following chemically induced pancreatitis in the mouse occurs predominantly through acinar cell dedifferentiation, whereby a genetic program resembling embryonic pancreatic precursors is reinstated.
Authors: David E Rosow; Andrew S Liss; Oliver Strobel; Stefan Fritz; Dirk Bausch; Nakul P Valsangkar; Janivette Alsina; Birte Kulemann; Joo Kyung Park; Junpei Yamaguchi; Jennifer LaFemina; Sarah P Thayer Journal: Surgery Date: 2012-07-06 Impact factor: 3.982
Authors: Claudia Cavelti-Weder; Maria Shtessel; Joshua E Reuss; Agnes Jermendy; Takatsugu Yamada; Francisco Caballero; Susan Bonner-Weir; Gordon C Weir Journal: Endocrinology Date: 2013-09-12 Impact factor: 4.736
Authors: Catherine Carrière; Alison L Young; Jason R Gunn; Daniel S Longnecker; Murray Korc Journal: Biochem Biophys Res Commun Date: 2009-03-16 Impact factor: 3.575