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| Status |
Public on Jul 19, 2011 |
| Title |
Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, while evidence supports the replicative capacity of adult beta cells in vivo, attempts at expanding human islet cells in tissue culture resulted in loss of beta-cell phenotype. Using a genetic lineage-tracing approach we have provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain a partially open chromatin structure in expanded BCD cells, although they are not transcribed. Here we report that BCD cells can be induced to redifferentiate by a combination of soluble factors. The redifferentiated cells express beta-cell genes, store insulin in typical secretory vesicles, and release it in response to glucose. The redifferentiation process involves mesenchymal-epithelial transition, as judged from changes in gene expression. Moreover, inhibition of the EMT effector SLUG using shRNA results in stimulation of redifferentiation. BCD cells also give rise at a low rate to cells expressing other islet hormones, suggesting transition through an islet progenitor-like stage during redifferentiation. These findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening.
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| Overall design |
Gene expression was studied in unexpanded islets (4 donors), expanded and dedifferentiated islet cells (4 donors), and re-differentiated islet cells (3 donors). The experiment was performed in 3 batches (see Date in the description table below).
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| Contributor(s) |
Russ HA, Sintov E, Anker-Kitai L, Friedman O, Lenz A, Toren G, Farhi C, Pasmanik-Chor M, Oron-Karni V, Ravassard P, Efrat S |
| Citation(s) |
21984932 |
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| Submission date |
Jul 18, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
[email protected]
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| Organization name |
Tel Aviv University
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| Department |
Biology
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| Lab |
Bioinformatics Unit
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| Street address |
Ramat Aviv
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| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA144355 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30732_RAW.tar |
40.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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