ArticleScientific reports2016
Redifferentiation of expanded human islet β cells by inhibition of ARX.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Article
- Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5.iScience · 2023Article
- Review
- Unlocking the post-transplant microenvironment for successful islet function and survival.Frontiers in endocrinology · 2023Review
- Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer.iScience · 2022Article
- Regenerative approaches to preserve pancreatic β-cell mass and function in diabetes pathogenesis.Endocrine · 2022Review
- Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative.Frontiers in medicine · 2021Review
- Loss of EGR-1 uncouples compensatory responses of pancreatic β cells.Theranostics · 2020Article
- Induction of α cell-restricted Gc in dedifferentiating β cells contributes to stress-induced β-cell dysfunction.JCI insight · 2019Article
- When β-cells fail: lessons from dedifferentiation.Diabetes, obesity & metabolism · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ex-vivo expansion of adult human islet β cells has been evaluated for generation of abundant insulin-producing cells for transplantation; however, lineage-tracing has demonstrated that this process results in β-cell dedifferentiation. Redifferentiation of β-cell-derived (BCD) cells can be achieved using a combination of soluble factors termed Redifferentiation Cocktail (RC); however, this treatment leads to redifferentiation of only a fraction of BCD cells. This study aimed at improving redifferentiation efficiency by affecting the balance of islet progenitor-cell transcription factors activated by RC treatment. Specifically, RC treatment induces the transcription factors PAX4 and ARX, which play key roles in directing pancreas endocrine progenitor cells into the β/δ or α/PP developmental pathways, respectively. Misactivation of ARX in RC-treated BCD cells may inhibit their redifferentiation into β cells. Blocking ARX expression by shRNA elevated insulin mRNA levels 12.8-fold, and more than doubled the number of insulin-positive BCD cells. ARX inhibition in expanded α-cell-derived cells treated with RC did not cause their transdifferentiation into insulin-producing cells. The combination of RC and ARX shRNA treatment may facilitate the generation of abundant insulin-producing cells for transplantation into patients with type 1 diabetes.
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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.