Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 919-928.e6 |
Journal | Cell Stem Cell |
Volume | 22 |
Issue number | 6 |
Early online date | 24 May 2018 |
DOIs | |
Publication status | Published - 1 Jun 2018 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Cell Differentiation
- Cells, Cultured
- Female
- Male
- Mice
- Pluripotent Stem Cells/cytology
- RNA, Long Noncoding/genetics
- X Chromosome/genetics
- X Chromosome Inactivation/genetics