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Series GSE69658 Query DataSets for GSE69658
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
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
BioProject PRJNA286114

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Supplementary file Size Download File type/resource
GSE69658_RAW.tar 33.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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