Digital reconstruction of full embryos during early mouse organogenesis

Peng Xie¹, Juan Shen², Yi Yang³, Xinrui Wang⁴, Wei Liu⁵, Hailong Cao³, Yanying Zheng³, Chen Wu³, Guangyao Mao³, Linjin Chen⁴, Jingjing He³, Weiheng Zheng³, Zepu Yang³, Xiao Zhang⁶, Xu Jiang³, Xianfa Yang⁷, Ke Fang³, Zhao Zhang², Xin Xue³, Xueting Chen², Chaoyi Wang², Xing Liu⁸, Ling Liu³, Xuebiao Yao⁸, Naihe Jing⁷, Wei Xie³, Jin Liu⁹, Hua Cao¹⁰, Zhuojuan Luo¹¹, Xiaodong Fang¹², Chengqi Lin¹³

Affiliations

¹ 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.
² Institute of Metagenomics, Qingdao-Europe Advanced Institute for Life Sciences, BGI Research, Qingdao 266555, China; BGI Research, Shenzhen 518081, China.
³ 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.
⁴ Medical Research Center and Reproductive Medicine Center, Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou 350001, China.
⁵ School of Mathematics, Sichuan University, Chengdu 610065, China.
⁶ School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China.
⁷ Guangzhou Laboratory, Guangzhou 510005, China.
⁸ MOE Key Laboratory for Cellular Dynamics, Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.
⁹ School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China. Electronic address: liujinlab@cuhk.edu.cn.
¹⁰ Medical Research Center and Reproductive Medicine Center, Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China. Electronic address: caohua69@fjmu.edu.cn.
¹¹ 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. Electronic address: zjluo@seu.edu.cn.
¹² BGI Research, Sanya 572027, China. Electronic address: fangxd@genomics.cn.
¹³ 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. Electronic address: cqlin@seu.edu.cn.

PMID: 40920635
DOI: 10.1016/j.cell.2025.05.035

Free article

Digital reconstruction of full embryos during early mouse organogenesis

Peng Xie et al. Cell. 2025.

Free article

. 2025 Aug 21;188(17):4754-4772.e18.

doi: 10.1016/j.cell.2025.05.035. Epub 2025 Jun 18.

Authors

Affiliations

¹ 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.
² Institute of Metagenomics, Qingdao-Europe Advanced Institute for Life Sciences, BGI Research, Qingdao 266555, China; BGI Research, Shenzhen 518081, China.
³ 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.
⁴ Medical Research Center and Reproductive Medicine Center, Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou 350001, China.
⁵ School of Mathematics, Sichuan University, Chengdu 610065, China.
⁶ School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China.
⁷ Guangzhou Laboratory, Guangzhou 510005, China.
⁸ MOE Key Laboratory for Cellular Dynamics, Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.
⁹ School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China. Electronic address: liujinlab@cuhk.edu.cn.
¹⁰ Medical Research Center and Reproductive Medicine Center, Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China. Electronic address: caohua69@fjmu.edu.cn.
¹¹ 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. Electronic address: zjluo@seu.edu.cn.
¹² BGI Research, Sanya 572027, China. Electronic address: fangxd@genomics.cn.
¹³ 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. Electronic address: cqlin@seu.edu.cn.

PMID: 40920635
DOI: 10.1016/j.cell.2025.05.035

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.

Keywords: cross-germ-layer signal communication; digital embryo; early organogenesis; primordium determination zone; single-cell 3D transcriptome; cardiac crescent.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Digital reconstruction of full embryos during early mouse organogenesis

Affiliations

Digital reconstruction of full embryos during early mouse organogenesis

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Molecular Biology Databases