Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration

Gastroenterology. 2005 Mar;128(3):728-41. doi: 10.1053/j.gastro.2004.12.008.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ceruletide
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation
  • Homeodomain Proteins / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mitosis
  • Pancreas / embryology*
  • Pancreas / physiopathology*
  • Pancreas, Exocrine / metabolism
  • Pancreas, Exocrine / physiopathology
  • Pancreatitis / chemically induced
  • Pancreatitis / genetics
  • Pancreatitis / metabolism
  • Pancreatitis / physiopathology*
  • Receptors, Notch
  • Regeneration*
  • Signal Transduction
  • Trans-Activators / metabolism


  • Homeodomain Proteins
  • Membrane Proteins
  • Nkx6-1 protein, mouse
  • Receptors, Notch
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Ceruletide