Document Detail

Cellular origins of adult human islet in vitro dedifferentiation.
MedLine Citation:
PMID:  18490899     Owner:  NLM     Status:  MEDLINE    
Cultured human islets can be dedifferentiated to duct-like structures composed mainly of cytokeratin+ and nestin+ cells. Given that these structures possess the potential to redifferentiate into islet-like structures, we sought to elucidate their specific cellular origins. Adenoviral vectors were engineered for beta-, alpha-, delta- or PP-cell-specific GFP expression. A double-stranded system was designed whereby cultures were infected with two vectors: one expressed GFP behind the cumate-inducible promoter sequence, and the other expressed the requisite transactivator behind the human insulin, glucagon, somatostatin or pancreatic polypeptide promoter. This system labels hormone+ cells in the islet in a cell-specific manner, allowing these cells to be tracked during the course of transformation from islet to duct-like structure. Post-infection, islets were cultured to induce dedifferentiation. Fluorescence microscopy demonstrated that alpha-, delta- and PP-cells contributed equally to the cytokeratin+ population, with minimal beta-cell contribution, whereas the converse was true for nestin+ cells. Complementary targeted cell ablation studies, using streptozotocin or similar adenoviral expression of the Bax (Bcl2-associated X protein) toxigene, validated these findings and suggested a redundancy between alpha-, delta- and PP-cells with respect to cytokeratin+ cell derivation. These results call into question the traditional understanding of islet cells as being terminally differentiated and provide support for the concept of adult islet morphogenetic plasticity.
Stephen C Hanley; Amélie Pilotte; Bernard Massie; Lawrence Rosenberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-19
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  88     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-24     Completed Date:  2008-08-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  761-72     Citation Subset:  IM    
Department of Surgery, McGill University, Montréal, QC, Canada.
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MeSH Terms
Adenoviridae / genetics
Cell Differentiation
Cells, Cultured
Genetic Vectors
Glucagon-Secreting Cells / cytology,  metabolism
Green Fluorescent Proteins / biosynthesis,  genetics
Insulin-Secreting Cells / cytology,  metabolism
Intermediate Filament Proteins / metabolism
Islets of Langerhans / cytology*,  metabolism
Keratins / metabolism
Nerve Tissue Proteins / metabolism
Pancreatic Ducts / cytology
Pancreatic Polypeptide-Secreting Cells / cytology,  metabolism
Promoter Regions, Genetic
Somatostatin / physiology
Somatostatin-Secreting Cells / cytology,  metabolism
Stem Cells / cytology
Streptozocin / pharmacology
bcl-2-Associated X Protein / biosynthesis,  genetics
Reg. No./Substance:
0/Intermediate Filament Proteins; 0/Nerve Tissue Proteins; 0/bcl-2-Associated X Protein; 0/nestin; 147336-22-9/Green Fluorescent Proteins; 18883-66-4/Streptozocin; 51110-01-1/Somatostatin; 68238-35-7/Keratins

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

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