 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 27, 2015 |
| Title |
Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
In-vitro expansion of functional adult human β-cells is an attractive approach for generating insulin-producing cells for transplantation. However, human islet cell expansion in culture results in loss of β-cell phenotype and epithelial-mesenchymal transition (EMT). This process activates expression of ZEB1 and ZEB2, two members of the zinc-finger homeobox family of E-cadherin repressors, which play key roles in EMT. Downregulation of ZEB1 using shRNA in expanded β-cell-derived (BCD) cells induced mesenchymal-epithelial transition (MET), β-cell gene expression, and proliferation attenuation. In addition, inhibition of ZEB1 expression potentiated redifferentiation induced by a combination of soluble factors, as judged by an improved response to glucose stimulation and a 3-fold increase in the fraction of C-peptide-positive cells to 60% of BCD cells. Furthermore, ZEB1 shRNA led to increased insulin secretion in cells transplanted in vivo. Our findings suggest that the effects of ZEB1 inhibition are mediated by attenuation of the miR-200c target genes SOX6 and SOX2. These findings, which were reproducible in cells derived from multiple human donors, emphasize the key role of ZEB1 in EMT in cultured BCD cells and support the value of ZEB1 inhibition for BCD cell redifferentiation and generation of functional human β-like cells for cell therapy of diabetes.
|
| |
|
| Overall design |
Effect of inhibition of ZEB1 on individual's islet cells gene expression.
|
| |
|
| Contributor(s) |
Sintov E, Nathan G, Knoller S, Russ HA, Pasmanik-Chor M, Efrat S |
| Citation(s) |
26264186 |
| Submission date |
Jun 08, 2015 |
| Last update date |
Oct 10, 2019 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
|
| Organization name |
Tel Aviv University
|
| Department |
Biology
|
| Lab |
Bioinformatics Unit
|
| Street address |
Ramat Aviv
|
| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
| |
|
| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
|
| Samples (8)
|
| GSM1705419 |
Expanded Islets- donor S106p6-Control |
| GSM1705420 |
Expanded Islets- donor S106p6-ZEB1 inhibition |
| GSM1705421 |
Expanded Islets- donor S114p7-Control |
| GSM1705422 |
Expanded Islets- donor S114p7-ZEB1 inhibition |
| GSM1705423 |
Expanded Islets- donor F32p6-Control |
| GSM1705424 |
Expanded Islets- donor F32p6-ZEB1 inhibition |
| GSM1705425 |
Expanded Islets- donor I51p6-Control |
| GSM1705426 |
Expanded Islets- donor I51p6-ZEB1 inhibition |
|
| Relations |
| BioProject |
PRJNA286114 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69658_RAW.tar |
33.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...