167P SnRNAseq analysis of muscle samples of patients with SMA reveals novel pathogenic pathways and open avenues for new therapeutic strategies

Spinal muscle atrophy (SMA) is a genetic disorder produced by mutations in the SMN1 gene leading to degeneration of lower motor neurones and, consequently, denervation of the skeletal muscles. The molecular pathways activated in the denervated muscles in humans are far to be known. We have applied s...

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Published in:Neuromuscular disorders : NMD 2024-10, Vol.43, p.104441, Article 104441.602
Main Authors: Collins, C., Gokul-Nath, R., Katsikis, P., Fernández-Simón, E., Villalobos, E., Monceau, A., Reza, M., Mehra, P., Laidler, Z., Clark, J., Rojas-García, R., Tasca, G., Marini-Bettolo, C., Diaz-Manera, J.
Format: Article
Language:English
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Summary:Spinal muscle atrophy (SMA) is a genetic disorder produced by mutations in the SMN1 gene leading to degeneration of lower motor neurones and, consequently, denervation of the skeletal muscles. The molecular pathways activated in the denervated muscles in humans are far to be known. We have applied single nuclei RNA sequencing (snRNAseq) to seven muscle samples of patients with genetically confirmed SMA type 3 with at least three copies of SMN2 gene and five age and gender matched controls. Bioinformatic analysis was performed to identify cell types present in muscle samples and changes in their gene expression profile. Metascape was used to identify the molecular pathways dysregulated in the different cell populations. We observed a statistically significant increase in nuclei expressing markers of satellite cells (6.5% vs 2.1%, p
ISSN:0960-8966
DOI:10.1016/j.nmd.2024.07.611