Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
Lab Invest. 2017 Oct;97(10):1133-1141. doi: 10.1038/labinvest.2017.87. Epub 2017 Sep 4.
In mammalian development, dynamic epigenetic reprogramming occurs in pre-implantation embryos and primordial germ cells and plays a critical role in conferring pluripotency on embryonic cells. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been derived and maintained in vitro under culture conditions that include stimulators and inhibitors of extrinsic signaling. Recent advances in stem cell cultivation have opened the possibility of capturing naive pluripotency, which is reminiscent of the pluripotency of inner cell mass cells, in vitro. However, emerging evidence has revealed complexity of epigenetic regulation in pluripotent stem cells in vitro that reflects the developmental stage, gender, and species. In this review, we describe the developmental potential and epigenetic regulation of pluripotent stem cells in rodents and humans in vitro and discuss unsolved issues in developing strategies to capture in vivo pluripotency in vitro.
在哺乳动物的发育过程中，动态的表观遗传重编程发生在着床前胚胎和原始生殖细胞中，并在赋予胚胎细胞多能性方面发挥着关键作用。多能干细胞，如胚胎干细胞和诱导多能干细胞，已经在体外培养条件下被分离和维持，这些培养条件包括外在信号的刺激物和抑制剂。最近在干细胞培养方面的进展为体外捕获原始多能性打开了可能性，这让人联想到内细胞团细胞的多能性。然而，新出现的证据揭示了体外多能干细胞中表观遗传调控的复杂性，这种复杂性反映了发育阶段、性别和物种。在这篇综述中，我们描述了体外啮齿动物和人类多能干细胞的发育潜力和表观遗传调控，并讨论了在开发体外捕获体内多能性的策略方面尚未解决的问题。
