ArticleScientific reports2015
Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Mechanisms inducing differentiation of adult islet progenitor-like cells into functional islet-like organoids.Frontiers in transplantation · 2026Article
- Imeglimin, unlike metformin, does not perturb differentiation of human induced pluripotent stem cells towards pancreatic β-like cells and rather enhances gain in β cell identity gene sets.Journal of diabetes investigation · 2025Article
- Review
- Regenerative approaches to preserve pancreatic β-cell mass and function in diabetes pathogenesis.Endocrine · 2022Review
- The miR-200-Zeb1 axis regulates key aspects of β-cell function and survival in vivo.Molecular metabolism · 2021Article
- Article
- MicroRNA-223 is essential for maintaining functional β-cell mass during diabetes through inhibiting both FOXO1 and SOX6 pathways.The Journal of biological chemistry · 2019Article
- ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes.Scientific reports · 2019Article
- Genetic dissection of the miR-200-Zeb1 axis reveals its importance in tumor differentiation and invasion.Nature communications · 2018Article
- The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.Clinical & experimental metastasis · 2018Review
- Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal transition in glioblastoma cells.Oncotarget · 2016Article
- TGFβ Pathway Inhibition Redifferentiates Human Pancreatic Islet β Cells Expanded In Vitro.PloS one · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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