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

Author

Listed:
  • Yongheng Fan

    (Chinese Academy of Sciences
    University of 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
    University of Chinese Academy of Sciences)

  • Bing Chen

    (Chinese Academy of Sciences)

  • Xiaoyu Xue

    (Chinese Academy of Sciences)

  • Haipeng Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhenni Chen

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Man Yin

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhifeng Xiao

    (Chinese Academy of Sciences)

  • Yannan Zhao

    (Chinese Academy of Sciences)

  • Jianwu Dai

    (Chinese Academy of Sciences)

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.

Suggested Citation

  • Yongheng Fan & Xianming Wu & Sufang Han & Qi Zhang & Zheng Sun & Bing Chen & Xiaoyu Xue & Haipeng Zhang & Zhenni Chen & Man Yin & Zhifeng Xiao & Yannan Zhao & Jianwu Dai, 2023. "Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40513-5
    DOI: 10.1038/s41467-023-40513-5
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    1. Xiaoyu Xue & Xianming Wu & Yongheng Fan & Shuyu Han & Haipeng Zhang & Yuting Sun & Yanyun Yin & Man Yin & Bing Chen & Zheng Sun & Shuaijing Zhao & Qi Zhang & Weiyuan Liu & Jiaojiao Zhang & Jiayin Li &, 2024. "Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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