Pasque Vincent, Plath Kathrin
Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Curr Opin Cell Biol. 2015 Dec;37:75-83. doi: 10.1016/j.ceb.2015.10.006. Epub 2015 Nov 11.
Dramatic epigenetic changes take place during mammalian differentiation from the naïve pluripotent state including the silencing of one of the two X chromosomes in female cells through X chromosome inactivation. Conversely, reprogramming of somatic cells to naive pluripotency is coupled to X chromosome reactivation (XCR). Recent studies in the mouse system have shed light on the mechanisms of XCR by uncovering the timing and steps of XCR during reprogramming to induced pluripotent stem cells (iPSCs), allowing the generation of testable hypotheses during embryogenesis. In contrast, analyses of the X chromosome in human iPSCs have revealed important differences between mouse and human reprogramming processes that can partially be explained by the establishment of distinct pluripotent states and impact disease modeling and the application of human pluripotent stem cells. Here, we review recent literature on XCR as a readout and determinant of reprogramming to pluripotency.
在哺乳动物从原始多能状态开始分化的过程中，会发生显著的表观遗传变化，包括通过X染色体失活使雌性细胞中的两条X染色体之一沉默。相反，将体细胞重编程为原始多能性与X染色体重新激活（XCR）相关联。小鼠系统中的最新研究通过揭示重编程为诱导多能干细胞（iPSC）过程中XCR的时间和步骤，阐明了XCR的机制，从而使得在胚胎发育过程中能够产生可检验的假设。相比之下，对人类iPSC中X染色体的分析揭示了小鼠和人类重编程过程之间的重要差异，这在一定程度上可以通过不同多能状态的建立来解释，并且会影响疾病建模以及人类多能干细胞的应用。在此，我们综述了有关XCR作为重编程为多能性的一个指标和决定因素的最新文献。
