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Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair

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  • Vishnu Muraleedharan Saraswathy

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Lili Zhou

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Mayssa H. Mokalled

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

Abstract

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.

Suggested Citation

  • Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50628-y
    DOI: 10.1038/s41467-024-50628-y
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