Résumé
The mammalian spinal cord and peripheral nervous system forge the links between the brain and the body to enable sensorimotor control. These functions are mediated by a diverse array of spinal cord cell types, each with their own molecular repertoires, morphology, activity, and contribution to behavior. Spinal neurons can also display differential vulnerabilities to disease or specific potential for plasticity, suggesting that cell type is a critical factor for understanding spinal cord pathophysiology. Key examples include that neurodegenerative diseases that affect the spinal cord such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are characterized by the loss of spinal motoneurons, while injured neurons display widely different regeneration depending on the cell type. To address the molecular basis of neuronal diversity in the spinal cord, we used single-nucleus RNA sequencing to profile the mouse and human adult spinal cord. Within human motoneurons, we observed a unique gene expression signature that provides insight into the selective degeneration of motoneurons. Within the mouse spinal cord, we profiled the spared tissue distal to an injury and discovered rare populations of spinal neurons that express regeneration-associated genes and undergo sprouting outgrowth and remodeling after injury. Ultimately, we hope that our work will provide fundamental knowledge and enhanced therapeutic targets in spinal cord injury and disease.