A Cellular Taxonomy of the Adult Human Spinal Cord

Abstract

Abstract The mammalian spinal cord functions as a community of glial and neuronal cell types to accomplish sensory processing, autonomic control, and movement; conversely, the dysfunction of these cell types following spinal cord injury or disease states can lead to chronic pain, paralysis, and death. While we have made great strides in understanding spinal cellular diversity in animal models, it is crucial to characterize human biology directly to uncover specialized features of basic function and to illuminate human pathology. Here, we present a cellular taxonomy of the adult human spinal cord using single nucleus RNA-sequencing with spatial transcriptomics and antibody validation. We observed 29 glial clusters, including rare cell types such as ependymal cells, and 35 neuronal clusters, which we found are organized principally by anatomical location. To demonstrate the potential of this resource for understanding human disease, we analyzed the transcriptome of spinal motoneurons that are prone to degeneration in amyotrophic lateral sclerosis (ALS) and other diseases. We found that, compared with all other spinal neurons, human motoneurons are defined by genes related to cell size, cytoskeletal structure, and ALS, thereby supporting a model of a specialized motoneuron molecular repertoire that underlies their selective vulnerability to disease. We include a publicly available browsable web resource with this work, in the hope that it will catalyze future discoveries about human spinal cord biology.