The role of DNA demethylation in liver to pancreas transdifferentiation

Author:

Har-Zahav Adi,Lixandru DanielaORCID,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

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)

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