Surani M Azim, Hayashi Katsuhiko, Hajkova Petra
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Cell. 2007 Feb 23;128(4):747-62. doi: 10.1016/j.cell.2007.02.010.
Genetic and epigenetic mechanisms regulate the transition from the totipotent zygote to pluripotent primitive ectoderm cells in the inner cell mass of mouse blastocysts. These pluripotent cells can be propagated indefinitely in vitro, underpinned by a unique epigenetic state. Following implantation of the blastocyst, diverse epigenetic modifiers control differentiation of pluripotent epiblast cells into somatic cells, while specification of germ cells requires repression of the somatic program. Regenerating totipotency during development of germ cells entails re-expression of pluripotency-specific genes and extensive erasure of epigenetic modifications. Increasing knowledge of key underlying mechanisms heightens prospects for creating pluripotent cells directly from adult somatic cells.
遗传和表观遗传机制调控着从全能合子向小鼠囊胚内细胞团中多能原始外胚层细胞的转变。这些多能细胞能够在体外无限增殖,其基础是一种独特的表观遗传状态。囊胚着床后,多种表观遗传修饰因子控制着多能上胚层细胞向体细胞的分化,而生殖细胞的特化则需要抑制体细胞程序。在生殖细胞发育过程中恢复全能性需要重新表达多能性特异性基因,并广泛擦除表观遗传修饰。对关键潜在机制的了解不断增加,提高了直接从成体体细胞创造多能细胞的前景。