The role of DNA demethylation in liver to pancreas transdifferentiation

• Published in: Stem cell research & therapy Vol. 13; no. 1; pp. 1 - 476
• Main Authors: Har-Zahav, Adi, Lixandru, Daniela, Cheishvili, David, Matei, Ioan Valentin, Florea, Ioana Raluca, Aspritoiu, Veronica Madalina, Blus-Kadosh, Inna, Meivar-Levy, Irit, Serban, Andreea Madalina, Popescu, Irinel, Szyf, Moshe, Ferber, Sarah, Dima, Simona Olimpia
• Format: Journal Article
• Language: English
• Published: London BioMed Central 16.09.2022; BMC
• Subjects: Adenoviruses; Chromatin; Demethylation; DNA methylation; Epigenetic modifications; Epigenetics; Gene expression; Hepatocytes; Infections; Insulin; Liver; Pancreas; Pancreatic transcription factors; Proteins; Regenerative medicine; Software; Transcription factors; Transdifferentiation; United States > US
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-022-03159-6

Abstract Background Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. Results The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. Conclusions Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.