Document Detail


Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro.
MedLine Citation:
PMID:  19208356     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Exocrine acinar cells in the pancreas are highly differentiated cells that retain a remarkable degree of plasticity. After isolation and an initial phase of dedifferentiation in vitro, rodent acinar cells can convert to endocrine beta-cells when cultured in the presence of appropriate factors. The mechanisms regulating this phenotypic conversion are largely unknown. METHODS: Using rat acinar cell cultures, we studied the role of Notch signaling in a model of acinar-to-beta-cell conversion. RESULTS: We report a novel lectin-based cell labeling method to demonstrate the acinar origin of newly formed insulin-expressing beta-cells. This method allows for specific tracing of the acinar cells. We demonstrate that growth factor-induced conversion of adult acinar cells to beta-cells is negatively regulated by Notch1 signaling. Activated Notch1 signaling prevents the reexpression of the proendocrine transcription factor Neurogenin-3, the key regulator of endocrine development in the embryonic pancreas. Interfering with Notch1 signaling allows modulating the acinar cell susceptibility to the differentiation-inducing factors. Its inhibition significantly improves beta-cell neoformation with approximately 30% of acinar cells that convert to beta-cells. The newly formed beta-cells mature when transplanted ectopically and are capable of restoring normal blood glycemia in diabetic recipients. CONCLUSIONS: We report for the first time an efficient way to reprogram one third of the acinar cells to beta-cells by adult cell type conversion. This could find application in cell replacement therapy of type 1 diabetes, provided that it can be translated from rodent to human models.
Authors:
Luc Baeyens; Stefan Bonné; Tomas Bos; Ilse Rooman; Cindy Peleman; Tony Lahoutte; Michael German; Harry Heimberg; Luc Bouwens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-27
Journal Detail:
Title:  Gastroenterology     Volume:  136     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1750-60.e13     Citation Subset:  AIM; IM    
Affiliation:
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Transdifferentiation / physiology*
Cells, Cultured
Insulin-Secreting Cells / cytology*
Male
Mice
Mice, Nude
Pancreas, Exocrine / cytology*,  metabolism
RNA, Messenger / analysis
Rats
Rats, Wistar
Receptor, Notch1 / genetics,  metabolism,  physiology*
Signal Transduction*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, Notch1
Comments/Corrections
Comment In:
Gastroenterology. 2009 May;136(5):1499-502   [PMID:  19327730 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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