RNA expression profiling in lymphoblastoid cell lines from mutated and non‐mutated amyotrophic lateral sclerosis patients

Abstract Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of upper and lower motor neurons with an unknown etiology. The difficulty of recovering biological material from patients led to employ lymphoblastoid cell lines (LCLs) as a model for ALS because many pathways, typically located in neurons, are also activated in these cells. Methods To investigate the expression of coding and long non‐coding RNAs in LCLs, a transcriptomic profiling of sporadic ALS (SALS) and mutated patients ( FUS , TARDBP , C9ORF72 and SOD1 ) and matched controls was realized. Thus, differentially expressed genes (DEGs) were investigated among the different subgroups of patients. Peripheral blood mononuclear cells (PBMCs) were isolated and immortalized into LCLs via Epstein–Barr virus infection; RNA was extracted, and RNA‐sequencing analysis was performed. Results Gene expression profiles of LCLs were genetic‐background‐specific; indeed, only 12 genes were commonly deregulated in all groups. Nonetheless, pathways enriched by DEGs in each group were also compared, and a total of 89 Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were shared among all patients. Eventually, the similarity of affected pathways was also assessed when our data were matched with a transcriptomic profile realized in the PBMCs of the same patients. Conclusions We conclude that LCLs are a good model for the study of RNA deregulation in ALS.