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X chromosome inactivation in human pluripotent stem cells as a model for human development: back to the drawing board?
Human Reproduction Update ( IF 13.3 ) Pub Date : 2017-06-05 , DOI: 10.1093/humupd/dmx015
Mieke Geens , Susana M. Chuva De Sousa Lopes

Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female cells. XCI is important for proper development and aberrant XCI has been linked to several pathologies. Recently, novel data obtained using high throughput single-cell technology during human preimplantation development have suggested that the XCI mechanism is substantially different from XCI in mouse. It has also been suggested that hPSC show higher complexity in XCI than the mouse. Here we compare the available recent data to understand whether XCI during human preimplantation can be properly recapitulated using hPSC.

中文翻译:

人类多能干细胞的X染色体失活作为人类发展的模型:回到图板?

人类多能干细胞(hPSC),无论是胚胎的还是诱导的(hESC和hiPSC),都被认为是人类早期发育的有价值的体外模型。为了履行这一诺言,重要的是这些细胞应尽可能在体内进行模拟在遗传和表观遗传水平上的分子事件。人类早期发育过程中最重要的表观遗传事件之一是X染色体失活(XCI),这是女性细胞中两个X染色体之一的转录沉默。XCI对于适当的开发很重要,异常的XCI已与多种病理联系在一起。最近,在人类植入前发育过程中使用高通量单细胞技术获得的新数据表明,XCI机制与小鼠XCI实质上不同。还建议hPSC在XCI中显示出比鼠标更高的复杂性。在这里,我们比较可用的最新数据,以了解使用hPSC是否可以正确地概括人类植入前的XCI。
更新日期:2017-06-05
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