XIST drives X-chromosome inactivation and safeguards female extraembryonic cells in humans.

XIST is required for X-chromosome inactivation establishment during in vitro differentiation of naive human pluripotent stem cells to trophoblast stem cells and extraembryonic mesoderm cells.

• Why it matters: Species-specific differences in XCI timing and regulation have left its role in human extraembryonic development unclear.
• What they did: In vitro differentiation to trophoblast stem cells and extraembryonic mesoderm cells is accompanied by XCI, with an inactive X chromosome showing an atypical chromatin state lacking DNA methylation and canonical heterochromatin marks. Loss-of-function experiments show XIST is required for XCI establishment, and XCI is temporally linked to extraembryonic differentiation.
• The result: XCI is needed for the survival of human female extraembryonic cells, linking XCI to formation of human extraembryonic lineages and implications for reproductive biology.