Self-organization of the in vitro attached human embryo

An in vitro model to study the early events that direct human embryo development after formation of the blastocyst and implantation in the uterine wall. Early-stage human embryo model Ali Brivanlou and colleagues have established an in vitro model to study the events that direct human embryo development between the formation of the blastocyst and implantation in the womb. They delineate key species-specific events during epiblast expansion, lineage segregation, trophoblast specification, bi-laminar disc formation and yolk sac cavitation. Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system 1 , 2 to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.