Single-nucleus transcriptomic atlas of spinal cord cells in human

Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and/or neural diseases, the underlying organization of its cells, including both neuronal and non-neuronal clusters remain elusive. Recently, several studies have attempted to define the cellular subtypes in the spinal cord and their functional heterogeneity using single-cell and/or single-nucleus RNA-sequencing in various animal models. However, molecular evidence of cellular heterogeneity in the adult human spinal cord has not yet been established. Here, we sought to classify spinal cord neurons and glial cells from human donors using high-throughput single-nucleus RNA-sequencing. Moreover, we compared the transcriptional patterns obtained in human samples with previously published single-nucleus transcriptomic profiles of the mouse spinal cord. The functional heterogeneity among the identified cell subtypes were also explored by Gene ontology (GO) term analysis. As a result, we generated the first comprehensive transcriptomic atlas of adult human spinal cord neurons and defined 24 neuronal clusters. For glial cells, astrocytes, microglia, and oligodendrocytes were divided into ten, eight, and eleven distinct transcriptomic subclusters, respectively. The comparison with mouse transcriptomic profiles revealed an overall similarity in the neuronal composition of the spinal cord between the two species, while simultaneously highlighting some degree of heterogeneity. In summary, these results illustrate the complexity and diversity of neuronal and glial types in the human spinal cord and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases. Overall design: Single-nucleus transcriptomic profiles of spinal cord cells in 3 human donors