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

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-07-05 DOI:10.1002/jgm.3711

Jessica Garau, Maria Garofalo, Francesca Dragoni, Eveljn Scarian, Rosalinda Di Gerlando, Luca Diamanti, Susanna Zucca, Matteo Bordoni, Orietta Pansarasa, Stella Gagliardi

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引用次数: 0

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.

Abstract Image

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突变和非突变肌萎缩侧索硬化症患者淋巴母细胞系的 RNA 表达谱分析。

背景：肌萎缩性脊髓侧索硬化症（ALS）是一种以上下运动神经元死亡为特征的神经退行性疾病，病因不明。由于很难从患者身上获取生物材料，因此淋巴母细胞系（LCL）被用作 ALS 的模型，因为这些细胞中也激活了许多通常位于神经元中的通路：为了研究编码RNA和长非编码RNA在LCLs中的表达，我们对散发性ALS（SALS）和突变患者（FUS、TARDBP、C9ORF72和SOD1）以及匹配的对照组进行了转录组学分析。因此，对不同亚组患者的差异表达基因（DEGs）进行了研究。通过 Epstein-Barr 病毒感染分离外周血单核细胞（PBMCs）并将其永生化为 LCLs；提取 RNA 并进行 RNA 序列分析：结果：LCLs的基因表达谱具有遗传背景特异性；事实上，只有12个基因在所有组别中普遍失调。然而，我们还比较了各组中 DEGs 丰富的通路，所有患者共有 89 个《京都基因与基因组百科全书》（KEGG）术语。最后，当我们的数据与同一患者的 PBMCs 中实现的转录组图谱相匹配时，受影响通路的相似性也得到了评估：我们得出结论：LCLs 是研究 ALS 中 RNA 失调的良好模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.