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.
方法:为了研究编码和长链非编码RNA在LCL中的表达,散发性ALS(SALS)和突变患者的转录组学分析(FUS,TARDBP,实现了C9ORF72和SOD1)和匹配的对照。因此,研究了不同亚组患者的差异表达基因(DEGs)。分离外周血单个核细胞(PBMC),并通过EB病毒感染永生化为LCL;提取RNA,并进行RNA测序分析。
结果:LCL的基因表达谱是遗传背景特异性的;确实,在所有群体中,只有12个基因普遍失调。尽管如此,还比较了每组DEGs富集的途径,所有患者共有89个京都基因和基因组百科全书(KEGG)术语。最终,当我们的数据与相同患者的PBMC中实现的转录组学图谱相匹配时,还评估了受影响通路的相似性.
结论:我们得出结论,LCL是研究ALS中RNA失调的良好模型。