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

Vishnu Muraleedharan Saraswathy, Lili Zhou and Mayssa H. Mokalled ()
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Vishnu Muraleedharan Saraswathy: Washington University School of Medicine
Lili Zhou: Washington University School of Medicine
Mayssa H. Mokalled: Washington University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50628-y

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