4.7 Article

The role of DNA demethylation in liver to pancreas transdifferentiation

Journal

STEM CELL RESEARCH & THERAPY
Volume 13, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13287-022-03159-6

Keywords

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

Funding

  1. Israel Science Foundation [1537 2016]
  2. Research Grants Dia-Cure [P 37 794, POC-A. 1-A.1.1.4-E-2015]

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The study examines the relationship between DNA methylation and liver to pancreas transdifferentiation. The results show that the transdifferentiation process is associated with DNA demethylation and increased expression of specific genes.
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.

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