ArticleStem cells and development2013
Reprogramming adult human dermal fibroblasts to islet-like cells by epigenetic modification coupled to transcription factor modulation.
Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Trial
- DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion.Bioinformatics (Oxford, England) · 2024Article
- Targeting DNA methylation and demethylation in diabetic foot ulcers.Journal of advanced research · 2023Review
- Reading between the (Genetic) Lines: How Epigenetics is Unlocking Novel Therapies for Type 1 Diabetes.Cells · 2020Review
- Review
- Liver to Pancreas Transdifferentiation.Current diabetes reports · 2019Review
- Epigenetic modification of mesenchymal stromal cells enhances their suppressive effects on the Th17 responses of cells from rheumatoid arthritis patients.Stem cell research & therapy · 2018Article
- Epigenetic Control of Endocrine Pancreas DifferentiationFrontiers in cell and developmental biology · 2018Review
- Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells.PloS one · 2018Article
- Computational methods for direct cell conversion.Cell cycle (Georgetown, Tex.) · 2016Review
- Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts.Stem cells international · 2016Article
- Multiple functions of Maf in the regulation of cellular development and differentiation.Diabetes/metabolism research and reviews · 2015Review
- DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In this article, we describe novel conditions for culture, expansion, and transdifferentiation of primary human dermal fibroblasts (hDFs) to induce expression of transcription factors (TFs) and hormones characteristic of the islets of Langerhans. We show that histones associated with the insulin gene are hyperacetylated and that insulin gene DNA is less methylated in islet cells compared to cells that do not express insulin. Using two compounds that alter the epigenetic signature of cells, romidepsin (Romi), a histone deacetylase inhibitor, and 5-Azacytidine (5-AzC), a chemical analogue of cytidine that cannot be methylated, we show that hDFs exhibit a distinctive regulation of expression of TFs involved in islet development as well as of induction of glucagon and insulin. Overexpression of Pdx1, a TF important for islet differentiation, and silencing of musculoaponeurotic fibrosarcoma oncogene homolog B, a TF that is expressed in mature glucagon-producing cells, result in induction of insulin to a higher level compared to Romi and 5-AzC alone. The cells obtained from this protocol exhibit glucose-stimulated insulin secretion and lower blood glucose levels of diabetic mice. These data show that fully differentiated nonislet-derived cells could be made to transdifferentiate to islet-like cells and that combining epigenetic modulation with TF modulation leads to enhanced insulin expression.
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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.