Division of Biology, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Semin Cell Dev Biol. 2011 Jun;22(4):336-42. doi: 10.1016/j.semcdb.2011.02.025. Epub 2011 Mar 3.
Acquisition of the pluripotent state coincides with epigenetic reprogramming of the X-chromosome. Female embryonic stem cells are characterized by the presence of two active X-chromosomes, cell differentiation by inactivation of one of the two Xs, and induced pluripotent stem cells by reactivation of the inactivated X-chromosome in the originating somatic cell. The tight linkage between X- and stem cell reprogramming occurs through pluripotency factors acting on noncoding genes of the X-inactivation center. This review article will discuss the latest advances in our understanding at the molecular level. Mouse embryonic stem cells provide a standard for defining the pluripotent ground state, which is characterized by low levels of the noncoding Xist RNA and the absence of heterochromatin marks on the X-chromosome. Human pluripotent stem cells, however, exhibit X-chromosome epigenetic instability that may have implications for their use in regenerative medicine. XIST RNA and heterochromatin marks on the X-chromosome indicate whether human pluripotent stem cells are developmentally 'naïve', with characteristics of the pluripotent ground state. X-chromosome status and determination thereof via noncoding RNA expression thus provide valuable benchmarks of the epigenetic quality of pluripotent stem cells, an important consideration given their enormous potential for stem cell therapy.
多能性状态的获得与 X 染色体的表观遗传重编程同时发生。雌性胚胎干细胞的特征是存在两条活性 X 染色体，细胞分化通过两条 X 染色体之一的失活来实现，而诱导多能干细胞则通过起始体细胞中失活 X 染色体的重新激活来实现。X 染色体和干细胞重编程之间的紧密联系是通过多能性因子作用于 X 失活中心的非编码基因来实现的。这篇综述文章将讨论我们在分子水平上理解的最新进展。小鼠胚胎干细胞为定义多能性基础状态提供了标准，其特征是非编码 Xist RNA 水平低，X 染色体上无异染色质标记。然而，人类多能干细胞表现出 X 染色体表观遗传不稳定性，这可能对其在再生医学中的应用具有重要意义。XIST RNA 和 X 染色体上的异染色质标记表明人类多能干细胞是否具有发育上的“幼稚”特征，具有多能性基础状态的特征。因此，X 染色体状态及其通过非编码 RNA 表达的确定为多能干细胞的表观遗传质量提供了有价值的基准，这是考虑到其在干细胞治疗中的巨大潜力的一个重要因素。
