| Cellular origins of adult human islet in vitro dedifferentiation. | |
| | |
MedLine Citation:
|
PMID: 18490899 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Stephen C Hanley; Amélie Pilotte; Bernard Massie; Lawrence Rosenberg |
Related Documents
:
|
11668039 - Downregulated in adenoma and putative anion transporter are regulated by cftr in cultur... 2192239 - Do the pancreatic primordial buds in embryogenesis have the potential to produce all pa... 9570939 - An immunohistochemical and morphometric analysis of insulin, insulin-like growth factor... 17237379 - Prevention of type 1 diabetes by invariant nkt cells is independent of peripheral cd1d ... 10218989 - Overexpression of insulin-like growth factor-ii in transgenic mice is associated with p... 2091879 - Streaming pancreas: islet cell kinetics. 20630949 - A two-step notch-dependant mechanism controls the selection of the polar cell pair in d... 22941419 - Proteoglycan synthesis and golgi organization in polarized epithelial cells. 14724189 - Roles of compatible osmolytes and heat shock protein 70 in the induction of tolerance t... |
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 |
Affiliation:
|
Department of Surgery, McGill University, Montréal, QC, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenoviridae
/
genetics Adult Cell Differentiation Cells, Cultured Genetic Vectors Glucagon-Secreting Cells / cytology, metabolism Green Fluorescent Proteins / biosynthesis, genetics Humans 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 |
| Chemical | |
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
Previous Document: Deterioration of atherosclerosis in mice lacking angiotensin II type 1A receptor in bone marrow-deri...
Next Document: Laser microdissection and primary cell cultures improve pharmacogenetic analysis in pancreatic adeno...