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| Status |
Public on Aug 27, 2014 |
| Title |
Redifferentiation of adult human β cells expanded in vitro by inhibition of the WNT pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In vitro expansion of adult human islet β cells is an attractive solution for the shortage of tissue for cell replacement therapy of type 1 diabetes. Using a lineage tracing approach, we have demonstrated that β-cell-derived (BCD) cells rapidly dedifferentiate in culture and can proliferate for up to 16 population doublings. Dedifferentiation is associated with changes resembling epithelial-mesenchymal transition (EMT). The WNT pathway has been shown to induce EMT and plays key roles in regulating replication and differentiation in many cell types. Here we show that BCD cell dedifferentiation is associated with β-catenin translocation into the nucleus and activation of the WNT pathway. Inhibition of β-catenin expression in expanded BCD cells using short hairpin RNA resulted in growth arrest, mesenchymal-epithelial transition, and redifferentiation, as judged by activation of β-cell gene expression. Furthermore, inhibition of β-catenin expression synergized with redifferentiation induced by a combination of soluble factors, as judged by an increase in the number of C-peptide-positive cells. Simultaneous inhibition of the WNT and NOTCH pathways also resulted in a synergistic effect on redifferentiation. These findings, which were reproducible in cells derived from multiple human donors, suggest that inhibition of the WNT pathway may contribute to a therapeutically applicable way for generation of functional insulin-producing cells following ex-vivo expansion.
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| Overall design |
Gene expression was studied for beta-cells (4 donors). Dedifferentiation was induced by inhibition of β-catenin expression using shRNA. The experiment was performed in 4 batches (see the 'Date' characteristic in the Sample records).
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| Contributor(s) |
Lenz A, Toren-Hartian G, Efrat S |
| Citation(s) |
25393025, 26418361 |
| Submission date |
Aug 26, 2014 |
| Last update date |
Jul 31, 2019 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
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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) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (12)
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| GSM1489097 |
Human adult beta cells, untreated, donor S108 |
| GSM1489098 |
Human adult beta cells, shRNA β-catenin 9, donor S108 |
| GSM1489099 |
Human adult beta cells, shRNA β-catenin 45, donor S108 |
| GSM1489100 |
Human adult beta cells, shRNA nontarget, donor S114 |
| GSM1489101 |
Human adult beta cells, untreated, donor S109 |
| GSM1489102 |
Human adult beta cells, shRNA β-catenin 9, donor S109 |
| GSM1489103 |
Human adult beta cells, shRNA β-catenin 45, donor S109 |
| GSM1489104 |
Human adult beta cells, shRNA β-catenin 9, donor S114 |
| GSM1489105 |
Human adult beta cells, untreated, donor S112 |
| GSM1489106 |
Human adult beta cells, shRNA β-catenin 9, donor S112 |
| GSM1489107 |
Human adult beta cells, shRNA β-catenin 45, donor S114, rep1 |
| GSM1489108 |
Human adult beta cells, shRNA β-catenin 45, donor S114, rep2 |
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| Relations |
| BioProject |
PRJNA259569 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60803_RAW.tar |
51.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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