DNA methylation remodeling in vitro and in vivo.
DNA methylation remodeling in vitro and in vivo.
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DOI：
10.1016/j.gde.2015.09.002
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发表时间：
2015-10
影响因子：
4
通讯作者：
Clark AT
中科院分区：
文献类型：
--
作者：
Clark AT
在哺乳动物体内，整体DNA去甲基化发生在胚胎着床前和原始生殖细胞（PGCs）中，假设它创造了一块空白石板或“白板”，上面写着新的DNA甲基化模式。然而，体内DNA的整体去甲基化远未完成，只有少数位点受到保护而不被去甲基化。去甲基化失败或明显的去甲基化导致分化受损。最近的研究表明，将引物的人类多能干细胞还原到naïve状态会导致不受控制的DNA去甲基化，这对体外培养的分化细胞的质量有未知的影响。总之，理解DNA甲基化重塑对于理解生命的表观遗传基础和再生医学干细胞的质量至关重要。
In mammals, global DNA demethylation in vivo occurs in the pre-implantation embryo and in primordial germ cells (PGCs) where it is hypothesized to create a blank slate or “tabula rasa” upon which new DNA methylation patterns are written. However, global DNA demethylation in vivo is far from complete with a small number of loci protected from demethylation. Failure to demethylate, or overt demethylation results in compromised differentiation. Recent work has shown that reversion of primed human pluripotent stem cells to the naïve state leads to unbridled DNA demethylation which has unknown consequences on the quality differentiated cells created in vitro. Taken together understanding DNA methylation remodeling is critical for understanding the epigenetic foundations of life, and the quality of stem cells for regenerative medicine.