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Stem Cell Res. 2011 Mar;6(2):187-93. doi: 10.1016/j.scr.2010.12.001. Epub 2010 Dec 13.

Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells.

Author information

1
Stem Cell Unit, Department of Genetics, Institute of Life Sciences, The Hebrew University, Edmund J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.

Abstract

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.

PMID:
21276761
DOI:
10.1016/j.scr.2010.12.001
[Indexed for MEDLINE]
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