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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)919-928.e6
JournalCell Stem Cell
Volume22
Issue number6
Early online date24 May 2018
DOIs
Publication statusPublished - 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

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