Zaveri Lamuk, Dhawan Jyotsna
Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India.
CSIR - Centre for Cellular and Molecular Biology, Hyderabad, India.
Front Cell Dev Biol. 2018 Jun 19;6:57. doi: 10.3389/fcell.2018.00057. eCollection 2018.
Pluripotent stem cells are characterized by their high proliferative rates, their ability to self-renew and their potential to differentiate to all the three germ layers. This rapid proliferation is brought about by a highly modified cell cycle that allows the cells to quickly shuttle from DNA synthesis to cell division, by reducing the time spent in the intervening gap phases. Many key regulators that define the somatic cell cycle are either absent or exhibit altered behavior, allowing the pluripotent cell to bypass cell cycle checkpoints typical of somatic cells. Experimental analysis of this modified stem cell cycle has been challenging due to the strong link between rapid proliferation and pluripotency, since perturbations to the cell cycle or pluripotency factors result in differentiation. Despite these hurdles, our understanding of this unique cell cycle has greatly improved over the past decade, in part because of the availability of new technologies that permit the analysis of single cells in heterogeneous populations. This review aims to highlight some of the recent discoveries in this area with a special emphasis on different states of pluripotency. We also discuss the highly interlinked network that connects pluripotency factors and key cell cycle genes and review evidence for how this interdependency may promote the rapid cell cycle. This issue gains translational importance since disruptions in stem cell proliferation and differentiation can impact disorders at opposite ends of a spectrum, from cancer to degenerative disease.
多能干细胞的特征在于其高增殖率、自我更新能力以及分化为所有三个胚层的潜力。这种快速增殖是由高度修饰的细胞周期实现的，该细胞周期通过减少在中间间隙期所花费的时间，使细胞能够快速从DNA合成进入细胞分裂。许多定义体细胞周期的关键调节因子要么不存在，要么表现出改变的行为，这使得多能细胞能够绕过体细胞典型的细胞周期检查点。由于快速增殖与多能性之间存在紧密联系，对这种修饰的干细胞周期进行实验分析一直具有挑战性，因为对细胞周期或多能性因子的干扰会导致细胞分化。尽管存在这些障碍，但在过去十年中，我们对这种独特细胞周期的理解有了很大提高，部分原因是出现了允许分析异质群体中单个细胞的新技术。本综述旨在强调该领域的一些最新发现，特别关注多能性的不同状态。我们还将讨论连接多能性因子和关键细胞周期基因的高度相互关联的网络，并回顾这种相互依赖性如何促进快速细胞周期的证据。由于干细胞增殖和分化的破坏会影响从癌症到退行性疾病等一系列相反极端的疾病，这个问题具有转化医学的重要性。
