期刊
CELL STEM CELL
卷 22, 期 6, 页码 919-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.05.001
关键词
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资金
- Wellcome Trust Fellowship [WT101861]
- Portuguese Foundation for Science and Technology, FCT [SFRH/BD/52197/2013]
- MRC Ph.D. studentships [1233706, 1509066]
A hallmark of naive pluripotency is the presence of two active X chromosomes in females. It is not clear whether prevention of X chromosome inactivation (XCI) is mediated by gene networks that preserve the naive state. Here, we show that robust naive pluripotent stem cell (nPSC) self-renewal represses expression of Xist, the master regulator of XCI. We found that nPSCs accumulate Xist on the male X chromosome and on both female X chromosomes as they become NANOG negative at the onset of differentiation. This is accompanied by the appearance of a repressive chromatin signature and partial X-linked gene silencing, suggesting a transient and rapid XCI-like state in male nPSCs. In the embryo, Xist is transiently expressed in males and in females from both X chromosomes at the onset of naive epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by destabilization of naive identity, suggesting that gender-specific mechanisms follow, rather than precede, XCI initiation.
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