Document Detail


Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreas.
MedLine Citation:
PMID:  22146645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Notch signaling pathway regulates embryonic development of the pancreas, inhibiting progenitor differentiation into exocrine acinar and endocrine islet cells. The adult pancreas appears to lack progenitor cells, and its mature cell types are maintained by the proliferation of pre-existing differentiated cells. Nonetheless, Notch remains active in adult duct and terminal duct/centroacinar cells (CACs), in which its function is unknown. We previously developed mice in which cells expressing the Notch target gene Hes1 can be labeled and manipulated, by expression of Cre recombinase, and demonstrated that Hes1(+) CACs do not behave as acinar or islet progenitors in the uninjured pancreas, or as islet progenitors after pancreatic duct ligation. In the current study, we assessed the function of Notch signaling in the adult pancreas by deleting the transcription factor partner of Notch, Rbpj, specifically in Hes1(+) cells. We find that loss of Rbpj depletes the pancreas of Hes1-expressing CACs, abrogating their ongoing contribution to growth and homeostasis of more proximal duct structures. Upon Rbpj deletion, CACs undergo a rapid transformation into acinar cells, suggesting that constitutive Notch activity suppresses the acinar differentiation potential of CACs. Together, our data provide direct evidence of an endogenous genetic program to control interconversion of cell fates in the adult pancreas.
Authors:
Daniel Kopinke; Marisa Brailsford; Fong Cheng Pan; Mark A Magnuson; Christopher V E Wright; L Charles Murtaugh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-29
Journal Detail:
Title:  Developmental biology     Volume:  362     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-02-28     Revised Date:  2014-06-02    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  57-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Acinar Cells / metabolism
Animals
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Cell Differentiation / physiology
Histological Techniques
Homeodomain Proteins / metabolism*
Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
Mice
Oligonucleotides / genetics
Pancreas, Exocrine / physiology*
Phenotype*
Receptors, Notch / metabolism*
Signal Transduction / physiology*
Grant Support
ID/Acronym/Agency:
P01-DK42502/DK/NIDDK NIH HHS; R01 DK075072-05/DK/NIDDK NIH HHS; R01-DK075072/DK/NIDDK NIH HHS; U01 DK072473/DK/NIDDK NIH HHS; U01-DK072473/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Hes1 protein, mouse; 0/Homeodomain Proteins; 0/Immunoglobulin J Recombination Signal Sequence-Binding Protein; 0/Oligonucleotides; 0/Rbpj protein, mouse; 0/Receptors, Notch
Comments/Corrections

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