Digital reconstruction of full embryos during early mouse organogenesis
Peng Xie, Juan Shen, Yi Yang, Xinrui Wang, Wei Liu, Hailong Cao, Yanying Zheng, Chen Wu, Guangyao Mao, Linjin Chen, Jingjing He, Weiheng Zheng, Weiheng Zheng, Xiao Zhang, Xu Jiang, Xianfa Yang, Ke Fang, Ke Fang, Xin Xue, Xueting Chen, Chaoyi Wang, Xing Liu, Ling Liu, Xuebiao Yao, Naihe Jing, Wei Xie, Jin Liu, Hua Cao, Zhuojuan Luo, Xiaodong Fang, Chengqi Lin, Xiaodong Fang, Chengqi Lin
Abstract
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.