Xu Yang
Cell Cycle. 2005 Mar;4(3):363-4. doi: 10.4161/cc.4.3.1529. Epub 2005 Mar 6.
Embryonic stem cells (ESCs) are capable of unlimited self-renewal and retain the pluripotency to differentiate into all cell lineages in the body. Since DNA damage occurs during normal cellular proliferation as well as after exposure to DNA damaging agents, it is critical for ESCs to possess stringent mechanisms to maintain genetic stability and prevent the passage of DNA damage to the progeny. Consistent with this notion, the rate of spontaneous mutation in ESCs is several magnitudes lower than that in somatic cells. Our recent findings indicate that tumor suppressor p53 plays an important role in maintaining genetic stability in ESCs by eliminating DNA-damaged ESCs from the replicative ESC pool. In this context, p53 induces the differentiation of DNA-damaged ESCs by directly suppressing the expression of Nanog, which is critical for the self-renewal of ESCs. This newly found role of p53 in cellular differentiation indicates an alternative mechanism for p53 to maintain genetic stability in ESCs and suggests the possibility that p53 might play a similar role in certain tissue stem cells and suppress the development of cancer stem cells.
胚胎干细胞（ESCs）能够无限自我更新，并保留分化为体内所有细胞谱系的多能性。由于DNA损伤在正常细胞增殖过程中以及暴露于DNA损伤剂后都会发生，因此胚胎干细胞拥有严格的机制来维持遗传稳定性并防止DNA损伤传递给子代至关重要。与这一观点一致，胚胎干细胞中的自发突变率比体细胞中的自发突变率低几个数量级。我们最近的研究结果表明，肿瘤抑制因子p53通过从复制性胚胎干细胞池中清除DNA损伤的胚胎干细胞，在维持胚胎干细胞的遗传稳定性方面发挥着重要作用。在这种情况下，p53通过直接抑制对胚胎干细胞自我更新至关重要的Nanog的表达，诱导DNA损伤的胚胎干细胞分化。p53在细胞分化中的这一新发现的作用表明了p53在胚胎干细胞中维持遗传稳定性的另一种机制，并暗示p53可能在某些组织干细胞中发挥类似作用并抑制癌症干细胞发展的可能性。
