DNA 去甲基化在肝向胰腺转分化中的作用。
The role of DNA demethylation in liver to pancreas transdifferentiation.
机构信息
Institute of Gastroenterology, Hepatology and Nutrition, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Sackler School of Medicine, Felsenstein Medical Research Center, Tel Aviv University, Tel Aviv, Israel.
出版信息
Stem Cell Res Ther. 2022 Sep 16;13(1):476. doi: 10.1186/s13287-022-03159-6.
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.
背景
由肝细胞转分化产生的胰岛素分泌细胞，可以作为再生医学的一个有吸引力的来源。本研究评估了 DNA 甲基化 pTFs 诱导肝向胰腺转分化之间的关系。
结果
转分化过程与 DNA 去甲基化有关，主要发生在基因调控位点，并伴有这些基因的表达增加。DNA 甲基化的主动抑制促进了胰腺转录因子诱导的转分化过程，支持 DNA 去甲基化在这一过程中的因果关系。
结论
转分化与全基因组 DNA 低甲基化和特定去甲基化基因的表达增加有关。组合使用表观遗传调节剂可能会增加胰腺转录因子的染色质可及性，从而提高发育过程的效率。
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