XIST drives X-chromosome inactivation and safeguards female extraembryonic cells in humans
Year: 2026
Type: article
Abstract: X-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 in vitro 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 needed 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.
Source: Nature Communications
Authors: Amitesh Panda, Léo Carrillo, Bradley Philip Balaton, Jeanne Brouillet, Solomon Nshemereirwe, Jarne Bonroy, Charbel Alfeghaly, Romina Facchinello, Sherif Khodeer, Nicolas Peredo, Ruben Boers, Gael Castel, Charlie London, Emmanuel Cazottes, Madeleine Moscatelli, Raissa Songwa Tchinda, Thi Xuan Ai Pham, San Kit To, Ryan Nicolaas Allsop, Yang Wang, Desislava Staneva, Peter J. Rugg-Gunn, Kathy K. Niakan, Joost Gribnau, Jean-François Ouimette, Claire Rougeulle, Vincent Pasque
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7223175752