Spatiotemporal dynamics of neuron differentiation and migration in the developing human spinal cord

Yuan Yu; Mengjie Pan; Quanyou Cai; Ziyu Feng; Baomei Cai; Kaixuan Lin; Shangtao Cao; Mingwei Min; Lihui Lin; Yanlin Ma; Jiekai Chen

doi:10.1016/j.jgg.2025.08.004

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Spatiotemporal dynamics of neuron differentiation and migration in the developing human spinal cord

doi: 10.1016/j.jgg.2025.08.004

a. Center for Cell Lineage Atlas, Center for Biomedical Digital Science, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China;
c. Guangzhou National Laboratory, Guangzhou, Guangdong 510320, China;
d. The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 511436, China;
e. Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 571199, China;
f. Department of Reproductive Medicine, Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 571101, China;
g. Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;
h. Guangzhou Medical University, Guangzhou, Guangdong 511436, China;
i. Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, China

Funds:

D Program of China (2024YFA1802300 and 2023YFF1204701), the National Natural Science Foundation of China (32225012 and 32200662), Major Project of Guangzhou National Laboratory (GZNL2023A02005), Pearl River Talent Recruitment Program (2021ZT09Y233), Science and Technology Planning Project of Guangdong Province, China (2023B1212060050 and 2023B1212120009), and Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR, P. R. China.

This work was financially supported by the National Key R&

Received Date: 2025-04-03
Accepted Date: 2025-08-10
Rev Recd Date: 2025-08-10

Available Online: 2025-08-19

Abstract

Abstract

Precise formation of complex neural circuits in the spinal cord, achieved through the integration of diverse neuronal populations, is essential for central nervous system function. However, the specialization and migration of human spinal cord neurons remain poorly understood. In this study, we perform single-cell transcriptome sequencing of human spinal cord from Carnegie Stage (CS) 16-21 and mouse spinal cord from embryonic day (E) 8.0-11.5, complemented by in situ sequencing of human spinal cord (CS 16-20). Our results reveal the critical role of the precursor state in neuronal differentiation and migration, identifying key transcription factors that regulate these processes across species. Notably, each neuronal lineage expresses unique markers as early as the progenitor stage at the spinal cord midline, and subsequently undergoes a shared transcriptional program during precursor commitment that guides migration. This synchronized migration, validated by spatial transcriptomics, occurs in both dorsal and ventral regions. Our findings offer important insights into the migration patterns and regulatory factors that guide spinal cord neuron subtype specification during embryogenesis.
- Human embryo spinal cord,
- Neurogenesis,
- In situ sequencing,
- Single-cell RNA sequencing,
- Cross-species

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References(48)

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