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 naive epiblast cells readily make trophectoderm. Inhibition of ERK signalling, instrumental in naive 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.

中文翻译：

---

人类天真上皮细胞具有无限的沿袭潜力

经典的小鼠胚胎学已建立了由连续谱系分歧驱动的早期发育范例。因此，源自早期上皮细胞的小鼠胚胎干细胞丧失了产生胚外滋养外胚层的能力。相反，我们显示出人类幼稚的成骨细胞容易使滋养外胚层。抑制ERK信号，有助于幼稚干细胞的繁殖，出乎意料地增强了滋养外胚层的形成，通过抑制淋巴结可以增强这种作用。转录组分析验证了向滋养层的转化，并随后产生了滋养滋养层细胞，滋养细胞和滋养细胞干细胞。遗传扰动表明，NANOG可以抑制，而TFAP2C可以诱导滋养外胚层。与植入后的进展一致，滋养外胚层的潜力在传统的人类多能干细胞中消失了，而后者却能制造羊膜。最后，来自晚期胚泡的人类胚胎上皮细胞有效产生滋养外胚层和分化的滋养层。因此，人类胚胎中的多能细胞在植入前会保留胚外谱系可塑性和再生潜力。利用这种意想不到的调节能力可能对辅助生殖技术有益。