Haemato-Oncology Research Unit, Division of Molecular Pathology, Division of Cancer Biology, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Stem Cell Reports. 2013 Sep 26;1(4):360-9. doi: 10.1016/j.stemcr.2013.08.005. eCollection 2013.
Cell division is a process by which a mother cell divides into genetically identical sister cells, although sister cells often display considerable diversity. In this report, over 350 sister embryonic stem cells (ESCs) were isolated through a microdissection method, and then expression levels of 48 key genes were examined for each sister cell. Our system revealed considerable diversities between sister ESCs at both pluripotent and differentiated states, whereas the similarity between sister ESCs was significantly elevated in a 2i (MEK and GSK3b inhibitors) condition, which is believed to mimic the ground state of pluripotency. DNA methyltransferase 3a/3b were downregulated in 2i-grown ESCs, and the loss of DNA methyltransferases was sufficient to generate nearly identical sister cells. These results suggest that DNA methylation is a major cause of the diversity between sister cells at the pluripotent states, and thus demethylation per se plays an important role in promoting ESC's self-renewal.
细胞分裂是一个母细胞分裂为遗传上相同的姐妹细胞的过程，尽管姐妹细胞通常表现出相当大的多样性。在本报告中，通过显微解剖方法分离了超过 350 个姐妹胚胎干细胞（ESCs），然后检查了每个姐妹细胞中 48 个关键基因的表达水平。我们的系统揭示了多能性和分化状态下姐妹 ESCs 之间的相当大的多样性，而在 2i（MEK 和 GSK3b 抑制剂）条件下，姐妹 ESCs 之间的相似性显著提高，这被认为模拟了多能性的基础状态。DNA 甲基转移酶 3a/3b 在 2i 培养的 ESCs 中下调，而 DNA 甲基转移酶的缺失足以产生几乎相同的姐妹细胞。这些结果表明，DNA 甲基化是多能状态下姐妹细胞之间多样性的主要原因，因此去甲基化本身在促进 ESC 自我更新中起着重要作用。
