PUBLICATION
Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair
- Authors
- Saraswathy, V.M., Zhou, L., Mokalled, M.H.
- ID
- ZDB-PUB-240816-1
- Date
- 2024
- Source
- Nature communications 15: 68086808 (Journal)
- Registered Authors
- Mokalled, Mayssa
- Keywords
- none
- Datasets
- GEO:GSE235395
- MeSH Terms
-
- Nerve Regeneration/physiology
- Recovery of Function
- Disease Models, Animal
- Animals, Genetically Modified
- Neuronal Plasticity*/physiology
- GABAergic Neurons/metabolism
- Spinal Cord Injuries*/metabolism
- Neurons/metabolism
- Neurons/physiology
- Spinal Cord*/metabolism
- Zebrafish*
- Neurogenesis*/genetics
- Animals
- Single-Cell Analysis*
- Spinal Cord Regeneration*
- CRISPR-Cas Systems
- PubMed
- 39147780 Full text @ Nat. Commun.
Citation
Saraswathy, V.M., Zhou, L., Mokalled, M.H. (2024) Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair. Nature communications. 15:68086808.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping