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Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys

Author

Listed:
  • Xiaoyu Xue

    (Chinese Academy of Sciences)

  • Xianming Wu

    (Chinese Academy of Sciences)

  • Yongheng Fan

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

  • Shuyu Han

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

  • Haipeng Zhang

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

  • Yuting Sun

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

  • Yanyun Yin

    (Chinese Academy of Sciences)

  • Man Yin

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

  • Bing Chen

    (Chinese Academy of Sciences)

  • Zheng Sun

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

  • Shuaijing Zhao

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

  • Qi Zhang

    (Chinese Academy of Sciences)

  • Weiyuan Liu

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

  • Jiaojiao Zhang

    (Chinese Academy of Sciences)

  • Jiayin Li

    (Chinese Academy of Sciences)

  • Ya Shi

    (Chinese Academy of Sciences)

  • Zhifeng Xiao

    (Chinese Academy of Sciences)

  • Jianwu Dai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yannan Zhao

    (Chinese Academy of Sciences)

Abstract

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50564-x
    DOI: 10.1038/s41467-024-50564-x
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