Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells
Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells
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DOI：
10.1016/j.scr.2010.12.001
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发表时间：
2011-03-01
影响因子：
1.2
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
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作者：
Bruck, Tal;Benvenisty, Nissim
在哺乳动物中，X染色体失活（XCI）是其中两个X染色体之一在XIST表达后沉默的过程。小鼠雌性多能干细胞不表达Xist，并含有两条活性X染色体。然而，主要基于XIST表达的人胚胎干细胞（hESC）中XCI的分析并不确定。在这里，我们通过对21个女性hESC细胞系中X染色体上整套基因表达的荟萃分析，研究了hESC中的XCI。因此，我们可以将ES细胞系分为三类：无XCI的细胞系、具有完全XCI的细胞系和具有部分XCI的细胞系。X染色体的部分失活总是涉及染色体的中部，围绕XIST转录位点。通过等位基因特异性表达或DNA甲基化分析来验证XCI在一些细胞系中的状态。有趣的是，对10个女性人诱导多能干细胞（hiPSC）系的分析表明，X染色体失活具有相似的异质性，并且也可以归类为在hESC中检测到的相同的三个类别。因此，我们可以表明，在一些hiPSC系中，X染色体在重编程时被激活。基于我们的分析，我们提出了一个模型的动力学XCI在多能干细胞。(c)2010 Elsevier B.V.保留所有权利。
In mammals, X chromosome inactivation (XCI) is a process in which one of the two X chromosomes is silenced, following XIST expression. Mouse female pluripotent stem cells do not express Xist, and harbor two active X chromosomes. However, analysis of XCI in human embryonic stem cells (hESCs), mainly based on XIST expression, was not conclusive. Here, we studied XCI in hESCs by meta-analysis of the expression of the entire set of genes on the X chromosome in 21 female hESC lines. Thus, we could divide the ES cell lines into three categories: lines with no XCI, lines with full XCI, and lines with partial XCI. The partial inactivation of the X chromosome always involved the middle of the chromosome, surrounding the XIST transcription site. The status of XCI in some of the cell lines was validated by either allelic-specific expression or DNA methylation analysis. Interestingly, analysis of 10 female human-induced pluripotent stem cell (hiPSC) lines demonstrated similar heterogeneity in the inactivation of X chromosome and could also be classified into the same three categories detected in hESCs. Thus, we could show that in some hiPSC lines, the X chromosome was activated on reprogramming. Based on our analysis, we propose a model of the dynamics of XCI in pluripotent stem cells. (c) 2010 Elsevier B.V. All rights reserved.