Xie Peng, Shen Juan, Yang Yi, Wang Xinrui, Liu Wei, Cao Hailong, Zheng Yanying, Wu Chen, Mao Guangyao, Chen Linjin, He Jingjing, Zheng Weiheng, Yang Zepu, Zhang Xiao, Jiang Xu, Yang Xianfa, Fang Ke, Zhang Zhao, Xue Xin, Chen Xueting, Wang Chaoyi, Liu Xing, Liu Ling, Yao Xuebiao, Jing Naihe, Xie Wei, Liu Jin, Cao Hua, Luo Zhuojuan, Fang Xiaodong, Lin Chengqi
Department of Cardiac Surgery, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, School of Life Science and Technology, Southeast University, Nanjing 210096, China; Coinnovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Institute of Metagenomics, Qingdao-Europe Advanced Institute for Life Sciences, BGI Research, Qingdao 266555, China; BGI Research, Shenzhen 518081, China.
Cell. 2025 Aug 21;188(17):4754-4772.e18. doi: 10.1016/j.cell.2025.05.035. Epub 2025 Jun 18.
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.
早期器官发生是胚胎发育中的一个关键阶段，其特征是广泛的细胞命运特化以启动器官形成，但同时也对发育缺陷高度敏感。在这里，我们对来自六个E7.5 - E8.0胚胎的285个连续切片进行了分析，以在单细胞分辨率下生成早期器官发生过程中的完整时空转录组和信号图谱。通过开发SEU - 3D，我们重建了数字胚胎，能够在天然空间背景下研究区域化基因表达。我们建立了一种空间信息基因 - 细胞共嵌入方法，系统地表征了内胚层和中胚层衍生物的空间图谱，并阐明了跨胚层和细胞类型的信号网络。此外，我们鉴定了在E7.75沿着胚胎前 - 胚外界面形成的原基决定区（PDZ），并且发现协调的信号通讯有助于心脏原基的形成。总的来说，高分辨率的“数字胚胎”为早期器官发生提供了重要见解，并为研究发育和疾病提供了一个独特的空间平台。
