重编程
DNA甲基化
生物
DNA去甲基化
表观遗传学
肝再生
甲基化
细胞生物学
胚胎干细胞
去甲基化
再生(生物学)
5-羟甲基胞嘧啶
基因组印记
肝细胞
遗传学
DNA
基因
基因表达
体外
作者
Tal Falick Michaeli,Ofra Sabag,Batia Azria,Rimma Fok,Nathalie Abudi,Rinat Abramovitch,Jonathan Monin,Yuval Gielchinsky,Howard Cedar,Yehudit Bergman
标识
DOI:10.1073/pnas.2314885121
摘要
As a result of partial hepatectomy, the remaining liver tissue undergoes a process of renewed proliferation that leads to rapid regeneration of the liver. By following the early stages of this process, we observed dramatic programmed changes in the DNA methylation profile, characterized by both de novo and demethylation events, with a subsequent return to the original adult pattern as the liver matures. Strikingly, these transient alterations partially mimic the DNA methylation state of embryonic hepatoblasts (E16.5), indicating that hepatocytes actually undergo epigenetic dedifferentiation. Furthermore, Tet2/Tet3-deletion experiments demonstrated that these changes in methylation are necessary for carrying out basic embryonic functions, such as proliferation, a key step in liver regeneration. This implies that unlike tissue-specific regulatory regions that remain demethylated in the adult, early embryonic genes are programmed to first undergo demethylation, followed by remethylation as development proceeds. The identification of this built-in system may open targeting opportunities for regenerative medicine.
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