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Gastroenterology. 2005 Mar;128(3):728-41.

Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration.

Author information

1
Barbara Davis Center for Childhood Diabetes, U. Colorado, HSC, 4200 E. 9th Avenue, B140, Denver, Colorado 80262 USA. jan.jensen@uchsc.edu

Abstract

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.

PMID:
15765408
DOI:
10.1053/j.gastro.2004.12.008
[Indexed for MEDLINE]

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