| Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro. | |
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MedLine Citation:
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PMID: 19208356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Luc Baeyens; Stefan Bonné; Tomas Bos; Ilse Rooman; Cindy Peleman; Tony Lahoutte; Michael German; Harry Heimberg; Luc Bouwens |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-27 |
Journal Detail:
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Title: Gastroenterology Volume: 136 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-04 Completed Date: 2009-05-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 1750-60.e13 Citation Subset: AIM; IM |
Affiliation:
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Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/RNA, Messenger; 0/Receptor, Notch1 |
| Comments/Corrections | |
Comment In:
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Gastroenterology. 2009 May;136(5):1499-502
[PMID:
19327730
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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