title: Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells.
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.
authors.affiliation: Stem Cell Unit, Department of Genetics, Institute of Life Sciences, The Hebrew University, Edmund J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Bruck
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D000818:Animals; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA