Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males

Elsa J. Sousa, Hannah T. Stuart, Lawrence E. Bates, Mohammadmersad Ghorbani, Jennifer Nichols, Sabine Dietmann, José C.R. Silva

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17 Scopus citations

Abstract

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. Silva and colleagues report that the initiation of X chromosome inactivation takes place in males and on both X chromosomes in females. This is transient and rapid and is triggered by downregulation of naive pluripotent transcription factors during the onset of differentiation.

Original languageEnglish
Pages (from-to)919-928.e6
JournalCell Stem Cell
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

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    Sousa, E. J., Stuart, H. T., Bates, L. E., Ghorbani, M., Nichols, J., Dietmann, S., & Silva, J. C. R. (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