GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE261nnn/GSE261711/primaryOK200TranscriptomicsHomo sapiens Genome binding/occupancy profiling by high throughput sequencing Methylation profiling by high throughput sequencing OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261711GEOGSEfalseXIST Drives X-Chromosome Inactivation and Safeguards Female Extraembryonic Cells in HumansX-chromosome inactivation (XCI) is essential for extraembryonic tissue growth and embryo development in mice. 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. Furthermore, we show that XCI is key for the survival of human female extraembryonic cells. Together, these findings link XCI to the formation of human extraembryonic lineages, with important implications for human reproductive biology.2026/08/31GSE261711GSM8149364GSM8149365GSM8149362GSM8149363GSM8149366GSM8149367GSM8215743GSM8149360GSM8149361GSM8215742GSM8215741GSM8215703GSM8215747GSM8215746GSM8215702GSM8215701GSM8215745GSM8215700GSM8215744GSM8215707GSM8215706GSM8215749GSM8215705GSM8215704GSM8215748GSM9081211GSM8215709GSM9081212GSM9081213GSM8215708GSM9081214GSM8229338GSM8229337GSM8215750GSM8215710GSM8215699GSM8215754GSM8215698GSM8215753GSM8215752GSM8215751GSM8215713GSM8215712GSM8215755GSM8215711301731857324676261711Homo sapiens