Digital reconstruction of full embryos during early mouse organogenesis

Early organogenesis is a crucial stage in embryonic development, characterized by extensive cell fate specification to initiate organ formation but also by a high susceptibility to developmental defects. Here, we profiled 285 serial sections from six E7.5-E8.0 embryos to generate full spatiotemporal transcriptome and signal maps during early organogenesis at single-cell resolution. By developing SEU-3D, we reconstructed digital embryos, enabling investigation of regionalized gene expression in the native spatial context. We established a space-informed gene-cell co-embedding approach, systematically characterized the spatial atlas of endoderm and mesoderm derivatives, and elucidated signaling networks across germ layers and cell types. Furthermore, we characterized a primordium determination zone (PDZ) formed along the anterior embryonic-extraembryonic interface at E7.75, and it revealed that the coordinated signaling communications contribute to the formation of cardiac primordium. Collectively, the high-resolution "digital embryo" provides significant insights into early organogenesis and a unique spatial platform for studying development and diseases.