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Understanding fundamental principles that regulate the early human embryo has clinical value for reproductive technologies, congenital disease, and regenerative medicine. My lab and others have begun to uncover the molecular mechanisms controlling the first week of development but following implantation, we have very poor understanding beyond historic histological characterisations. We have learned a lot from the mouse, but human post-implantation development is very distinct from mouse. One example, following implantation a primate specific cell type fills the blastocoel cavity prior to gastrulation, the extra embryonic mesenchyme. This cell type is completely lacking in the mouse.New opportunities to study post-implantation development has emerged through extended blastocyst cultures and stem cell-based embryo models. In this project we will build a comprehensive spatial single cell transcriptional atlas of implantation, describing the cell types and the genes that control them. This resource will be critical to validate blastoids and post-implantation embryo models. Functionally we will use the transcriptional information and validated embryo models, together with genome editing to dissect regulators of the implantation event and lineage specification of the extra embryonic mesenchyme and amnion. Lastly, we will extend our recent studies of the epigenetic control through Polycomb Repressive Complex 2, histone deacetylation and X-chromosome inactivation in female embryos.