RRC ID 81420
Author Saraswathy VM, Zhou L, Mokalled MH.
Title Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.
Journal Nat Commun
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.
Volume 15(1)
Pages 6808
Published 2024-8-15
DOI 10.1038/s41467-024-50628-y
PII 10.1038/s41467-024-50628-y
PMID 39147780
PMC PMC11327264
MeSH Animals Animals, Genetically Modified CRISPR-Cas Systems Disease Models, Animal GABAergic Neurons / metabolism Nerve Regeneration / physiology Neurogenesis* / genetics Neuronal Plasticity* / physiology Neurons / metabolism Neurons / physiology Recovery of Function Single-Cell Analysis* Spinal Cord* / metabolism Spinal Cord Injuries* / metabolism Spinal Cord Regeneration* Zebrafish*
IF 12.121
Resource
Zebrafish Tg(vglut2a:lRl-GFP) Tg(gad1b:GFP)