TY - JOUR T1 - Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential JF - bioRxiv DO - 10.1101/2020.02.04.933812 SP - 2020.02.04.933812 AU - Ge Guo AU - Giuliano Giuseppe Stirparo AU - Stanley Strawbridge AU - Daniel Spindlow AU - Jian Yang AU - James Clarke AU - Anish Dattani AU - Ayaka Yanagida AU - Meng Amy Li AU - Sam Myers AU - Buse Nurten Özel AU - Jennifer Nichols AU - Austin Smith Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/07/2020.02.04.933812.abstract N2 - Classical mouse embryology has established a paradigm of early development driven by sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derived from early epiblast have lost the potency to produce extraembryonic trophectoderm. We show in contrast that human naïve epiblast cells readily make trophectoderm. Inhibition of ERK signalling, instrumental in naïve stem cell propagation, unexpectedly potentiates trophectoderm formation, an effect enhanced by Nodal inhibition. Transcriptome analyses authenticate conversion into trophectoderm with subsequent production of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Genetic perturbations indicate that NANOG suppresses and TFAP2C enables trophectoderm induction. Consistent with post-implantation progression, trophectoderm potential is extinguished in conventional human pluripotent stem cells, which instead make amnion. Finally, human embryo epiblasts from late blastocysts efficiently generate trophectoderm and differentiated trophoblast. Thus, pluripotent cells in the human embryo retain extraembryonic lineage plasticity and regenerative potential until implantation. Harnessing this unanticipated regulative capacity may be beneficial for assisted reproduction technology.Competing Interest StatementAS and GG are inventors on a patent application relating to human naive stem cells filed by the University of Cambridge. ER -