Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury

Yongheng Fan, Xianming Wu, Sufang Han, Qi Zhang, Zheng Sun, Bing Chen, Xiaoyu Xue, Haipeng Zhang, Zhenni Chen, Man Yin, Zhifeng Xiao (), Yannan Zhao () and Jianwu Dai ()
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Yongheng Fan: Chinese Academy of Sciences
Xianming Wu: Chinese Academy of Sciences
Sufang Han: South China Agricultural University
Qi Zhang: Chinese Academy of Sciences
Zheng Sun: Chinese Academy of Sciences
Bing Chen: Chinese Academy of Sciences
Xiaoyu Xue: Chinese Academy of Sciences
Haipeng Zhang: Chinese Academy of Sciences
Zhenni Chen: Chinese Academy of Sciences
Man Yin: Chinese Academy of Sciences
Zhifeng Xiao: Chinese Academy of Sciences
Yannan Zhao: Chinese Academy of Sciences
Jianwu Dai: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular dynamic responses and heterogeneity across different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to investigate the region-related cellular responses in female rhesus monkeys with complete thoracic SCI from acute to chronic phases. We found that distal lumbar tissue cells were severely impacted, leading to degenerative microenvironments characterized by disease-associated microglia and oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI. By implanting scaffold into the injury sites, we could improve the injury microenvironment through glial cells and fibroblast regulation while remodeling spared lumbar tissues via reduced inhibitory neurons proportion and improved phagocytosis and myelination. Our findings offer crucial pathological insights into the spared distal tissues and proximal tissues after SCI, emphasizing the importance of scaffold-based treatment approaches targeting heterogeneous microenvironments.

Date: 2023
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DOI: 10.1038/s41467-023-40513-5

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