First Author | Sousa EJ | Year | 2018 |
Journal | Cell Stem Cell | Volume | 22 |
Issue | 6 | Pages | 919-928.e6 |
PubMed ID | 29804891 | Mgi Jnum | J:316300 |
Mgi Id | MGI:6835495 | Doi | 10.1016/j.stem.2018.05.001 |
Citation | Sousa EJ, et al. (2018) Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males. Cell Stem Cell 22(6):919-928.e6 |
abstractText | 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. |