X chromosome inactivation (XCI) refers to the transcriptional repression of one of the two X chromosomes in female cells, and mediates dosage compensation between XY males and XX females (reviewed in (Kim et al., 2011)). Transcription of a long non-coding RNA, XIST (X-inactive specific transcript), has a role in initiating and maintaining XCI. In mice, female PSCs do not express Xist and have two active X chromosomes (XaXa); upon differentiation, Xist transcription is de-repressed on a single X chromosome, resulting in inactivation of that chromosome (XaXi). The process of XCI in humans also involves XIST, but the mechanisms controlling its expression are fundamentally different than those regulating Xist in mice (Migeon et al., 2002). While the “normal” state of XCI in hPSCs remains controversial, almost all reported female hPSC lines display some degree of XCI (Dvash et al., 2010; Hall et al., 2008; Hoffman et al., 2005; Pomp et al., 2011; Shen et al., 2008; Tchieu et al., 2010) with few exceptions (Lengner et al., 2010; Marchetto et al., 2010) (Hanna et al., 2010).
