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Although spinal muscular atrophy (SMA) is a motor neuron disease caused by the loss of survival of motor neuron proteins, there is growing evidence that lesions in nonmotor neuron cells are involved in SMA pathogenesis. Transcriptome alterations occurring at the single-cell level in SMA spinal cord are unknown. Here, we performed single-cell RNA sequencing of the spinal cord of a severe SMA mouse model, and characterized ten cell types as well as their differentially expressed genes. Using CellChat, we found that cellular communication between different cell types in the spinal cord of SMA mice is substantially reduced. A dimensionality reduction analysis revealed 29 cell subtypes and differentially expressed genes for each subtype. Among them, the most significant change in the SMA spinal cord at the single-cell level was observed in a subpopulation of vascular fibroblasts. This subpopulation was greatly reduced, which may be responsible for vascular defects in SMA mice and may lead to widespread reductions in protein synthesis and energy metabolism. This study is the first to report a single-cell atlas of the spinal cord of mice with severe SMA, providing new insights into SMA pathogenesis.

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