Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males.
Sousa, Elsa J
Cell stem cell
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Sousa, E. J., Stuart, H. T., Bates, L., Ghorbani, M., Nichols, J., Dietmann, S., & Rebelo Da Silva, J. (2018). Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males.. Cell stem cell, 22 (6), 919-928.e6. https://doi.org/10.1016/j.stem.2018.05.001
A hallmark of naïve cell identity is the presence of two active X-chromosomes in females. However, little is known if the naïve gene network prevents the initiation of Xchromosome- inactivation (XCI). Here, we demonstrate that robust naïve pluripotent stem cell (nPSC) self-renewal abolishes expression of Xist, the master regulator of XCI. Intriguingly, at the onset of differentiation when nPSCs become Nanog-negative they accumulate Xist on the male X-chromosome and on both female X-chromosomes. In fact, XCI occurs in males as characterised by appearance of a repressive chromatin signature and partial X-linked gene silencing, albeit transiently and rapidly. Likewise, in the embryo Xist is transiently expressed in males and in females from both Xchromosomes at the onset of epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by the destabilization of the naïve identity, which suggests that gender-specific mechanisms follow rather than precede XCI initiation.
Cells, Cultured, X Chromosome, Pluripotent Stem Cells, Animals, Mice, Cell Differentiation, Female, Male, X Chromosome Inactivation, RNA, Long Noncoding
This study was supported by a Wellcome Trust Fellowship (WT101861) to J.C.R.S., who is a Wellcome Trust Senior Research Fellow. E.J.S. is the recipient of a Ph.D. fellowship from the Portuguese Foundation for Sciences and Technology, FCT (SFRH/BD/52197/2013). H.T.S. and L.E.B. are recipients of an MRC Ph.D. studentship.
Wellcome Trust (101861/Z/13/Z)
Isaac Newton Trust (MINUTE 1322(e))
External DOI: https://doi.org/10.1016/j.stem.2018.05.001
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278620
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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