The role of DNA demethylation in liver to pancreas transdifferentiation

Adi Har-Zahav, Daniela Lixandru, David Cheishvili, Ioan Valentin Matei, Ioana Raluca Florea, Veronica Madalina Aspritoiu, Inna Blus-Kadosh, Irit Meivar-Levy, Andreea Madalina Serban, Irinel Popescu, Moshe Szyf, Sarah Ferber, Simona Olimpia Dima

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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.

Original languageEnglish
Article number476
JournalStem Cell Research and Therapy
Issue number1
StatePublished - 16 Sep 2022
Externally publishedYes

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  • Cell replacement therapy for diabetes
  • DNA methylation
  • Epigenetic modifications
  • Liver
  • Pancreas
  • Pancreatic transcription factors
  • Transdifferentiation


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