Despite the recognized importance of spinal cord in sensory processing, motor behaviors and/or neural diseases, the underlying neuronal clusters remain elusive. Recently, several studies attempted to define the neuronal types and functional heterogeneity in spinal cord using single cell and/or single-nucleus RNA-sequencing in varied animal models. However, the molecular evidence of neuronal heterogeneity in human spinal cord has not been established yet. Here we sought to classify spinal cord neurons from human donors by high-throughput single-nucleus RNA-sequencing. The functional heterogeneity of identified cell types and signaling pathways that connecting neuronal subtypes were explored. Moreover, we also compared human results with previous single-cell transcriptomic profiles of mouse spinal cord. As a result, we generated the first comprehensive atlas of human spinal cord neurons and defined 18 neuronal clusters. In addition to identification of the new and functionally-distinct neuronal subtypes, our results also provide novel marker genes for previously known neuronal types. The comparation with mouse transcriptomic profiles revealed an overall similarity in the cellular composition of spinal cord between the two species. In summary, these results illustrate the complexity and diversity of neuronal types in human spinal cord and will provide an important resource for future researches to explore the molecular mechanism underlying several spinal cord physiology and diseases.
A culture model for neurite regeneration of human spinal cord neurons