XIST Drives X-Chromosome Inactivation and Safeguards Female Extraembryonic Cells in Humans

However, species-specific differences in its timing and regulation have left its role in human development unclear. Here, we show that the differentiation of naive human pluripotent stem cells to trophoblast stem cells and extraembryonic mesoderm cells is accompanied by XCI.

The inactive X chromosome displays an atypical chromatin state, lacking DNA methylation and canonical heterochromatin marks. We demonstrate that extraembryonic differentiation and XCI are temporally linked. Using loss of function approaches, we found that XIST is required for XCI establishment in humans.