A mouse model demonstrates a single-cell atlas for severe spinal muscular atrophy (SMA) in the spinal cord, according to a recent study.

After running a dimensionality reduction analysis, the researchers identified a total of 29 cell types. Fibroblasts showcased the most differing pattern compared to normal tissue, with a marked decrease in the number of cells. This finding likely translates into impaired vascularization and diminished energy metabolism and protein synthesis.

“Through [single-cell RNA sequencing], we identified the disease-specific [differentially expressed genes] of each cell type and subtypes of SMA spinal cord and found that the decline in the number of vascular fibroblasts was most pronounced at the single-cell level,” the authors wrote.

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The results were published in the journal PLoS Genetics.

This experimental study used single-cell RNA sequencing of spinal cord tissue from a mouse model with severe SMA to determine the cell lines, quantities inside each cell subgroup, and gene expression, to later compare the data to control mice with a normal spinal cord.

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“The weakened interaction between vascular and central nervous system (CNS) cells in our findings also suggests that an abnormal blood vessel structure may lead to decreased material exchange with CNS cells, affecting spinal cord function to some extent,” the study team noted.

Astrocytes, on the other hand, exhibited increased ribosomal activity among the AS-4 reactive subtype in SMA vs control mice. Another subtype, the A1, was also present, and has been previously linked to other degenerative disorders of the nervous system by weakened synaptic and phagocytic functions.

As for oligodendrocytes (OL), the single-cell RNA sequence demonstrated the myelinating OL-5 subtype was affected the most. These cells had decreased protein synthesis while increasing myelination signaling pathways.

Finally, cellular communication was also deficient, as determined by a CellChat analysis. Both the amount and intensity among cells were lower in the SMA mice than in the control group. Notably, committed OL precursors and OL precursor cells had the lowest communication.


Sun J, Qiu J, Yang Q et al. Single-cell RNA sequencing reveals dysregulation of spinal cord cell types in a severe spinal muscular atrophy mouse model. PLoS Genet. Published online September 8, 2022. doi:10.1371/journal.pgen.1010392