ArticlePloS one2015
TGFβ Pathway Inhibition Redifferentiates Human Pancreatic Islet β Cells Expanded In Vitro.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Serum-free culture with PVP enables maintenance of primary culture of parathyroid cells in vitro.Bioscience reports · 2026Article
- Increased TGF-β/Activin-Smad2 signaling is associated with pancreatic β-cell dysfunction and glucose intolerance in gestational diabetes mellitus.Molecular metabolism · 2026Article
- Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing.Discover oncology · 2025Article
- Endoplasmic reticulum stress and forkhead box protein O1 inhibition mediate palmitic acid and high glucose-induced β-cell dedifferentiation.World journal of diabetes · 2025Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
- Review
- Regeneration of Pancreatic Beta Cells by Modulation of Molecular Targets Using Plant-Derived Compounds: Pharmacological Mechanisms and Clinical Potential.Current issues in molecular biology · 2023Review
- Review
- Bioengineered Pancreas-Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Optimizing Generation of Stem Cell-Derived Islet Cells.Stem cell reviews and reports · 2022Review
- HumanMine: advanced data searching, analysis and cross-species comparison.Database : the journal of biological databases and curation · 2022Article
- Review
- The miR-200-Zeb1 axis regulates key aspects of β-cell function and survival in vivo.Molecular metabolism · 2021Article
- TGF-β Signaling in Pancreatic Islet β Cell Development and Function.Endocrinology · 2021Review
- Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation.Endocrinology · 2020Article
- Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D.Molecular metabolism · 2020Article
- Induction of α cell-restricted Gc in dedifferentiating β cells contributes to stress-induced β-cell dysfunction.JCI insight · 2019Article
- Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes.Experimental and therapeutic medicine · 2018Review
- Long non-coding RNA MEG3 mediates high glucose-induced endothelial cell dysfunction.International journal of clinical and experimental pathology · 2018Article
- The undoing and redoing of the diabetic β-cell.Journal of diabetes and its complications · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In-vitro expansion of insulin-producing cells from adult human pancreatic islets could provide an abundant cell source for diabetes therapy. However, proliferation of β-cell-derived (BCD) cells is associated with loss of phenotype and epithelial-mesenchymal transition (EMT). Nevertheless, BCD cells maintain open chromatin structure at β-cell genes, suggesting that they could be readily redifferentiated. The transforming growth factor β (TGFβ) pathway has been implicated in EMT in a range of cell types. Here we show that human islet cell expansion in vitro involves upregulation of the TGFβ pathway. Blocking TGFβ pathway activation using short hairpin RNA (shRNA) against TGFβ Receptor 1 (TGFBR1, ALK5) transcripts inhibits BCD cell proliferation and dedifferentiation. Treatment of expanded BCD cells with ALK5 shRNA results in their redifferentiation, as judged by expression of β-cell genes and decreased cell proliferation. These effects, which are reproducible in cells from multiple human donors, are mediated, at least in part, by AKT-FOXO1 signaling. ALK5 inhibition synergizes with a soluble factor cocktail to promote BCD cell redifferentiation. The combined treatment may offer a therapeutically applicable way for generating an abundant source of functional insulin-producing cells following ex-vivo expansion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.