Molecular architecture of lineage allocation and tissue organization in early mouse embryo

During post-implantation development of the mouse embryo, descendants of the inner cell massin the early epiblasttransit from the naive to primed pluripotent state1. Concurrently, germ layersare formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mappingand lineage-analysis studies have revealed that cells in different regions of the germ layersacquire location-specific cell fates during gastrulation2–5. The regionalization of cell fates preceding the formation of the basic body plan—the mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational study—is conserved in vertebrate embryos6–8. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptomeof cell populations at defined positions in the germ layersduring development from pre- to late- gastrulationstages. This spatiotemporal transcriptomeprovides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptomefurther identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of Hippo–Yap signalling in germ-layer development and reveals the contribution of visceral endodermto the endodermin the early mouse embryo.