Mesh : Animals Zebrafish Spinal Cord Injuries / metabolism Single-Cell Analysis Spinal Cord Regeneration Neuronal Plasticity / physiology Neurogenesis / genetics Spinal Cord / metabolism Neurons / metabolism physiology CRISPR-Cas Systems GABAergic Neurons / metabolism Recovery of Function Disease Models, Animal Nerve Regeneration / physiology Animals, Genetically Modified

来  源:   DOI:10.1038/s41467-024-50628-y   PDF(Pubmed)

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.
摘要:
成年斑马鱼具有从严重脊髓损伤中恢复的先天能力。这里,我们报告了一个全面的单核RNA测序图集,跨越6周的再生。我们确定了脊髓修复过程中成人神经发生和神经元可塑性的协同作用。谷氨酸能和GABA能神经元的神经发生在损伤后恢复兴奋/抑制平衡。此外,损伤反应性神经元(iNeurons)的瞬时群体在损伤后1周显示出升高的可塑性。我们发现iNeuons是损伤后存活的神经元,在损伤后获得神经母细胞样基因表达特征。CRISPR/Cas9诱变表明,iNeurons是功能恢复所必需的,并采用囊泡运输作为神经元可塑性的基本机制。这项研究提供了指导脊髓再生的细胞和机制的综合资源,并建立了斑马鱼作为可塑性驱动的神经修复模型。
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