{"title":"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。","authors":"Jessica Garau, Maria Garofalo, Francesca Dragoni, Eveljn Scarian, Rosalinda Di Gerlando, Luca Diamanti, Susanna Zucca, Matteo Bordoni, Orietta Pansarasa, Stella Gagliardi","doi":"10.1002/jgm.3711","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>To investigate the expression of coding and long non-coding RNAs in LCLs, a transcriptomic profiling of sporadic ALS (SALS) and mutated patients (<i>FUS</i>, <i>TARDBP</i>, <i>C9ORF72</i> and <i>SOD1</i>) 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>We conclude that LCLs are a good model for the study of RNA deregulation in ALS.</p>\n </section>\n </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3711","citationCount":"0","resultStr":"{\"title\":\"RNA expression profiling in lymphoblastoid cell lines from mutated and non-mutated amyotrophic lateral sclerosis patients\",\"authors\":\"Jessica Garau, Maria Garofalo, Francesca Dragoni, Eveljn Scarian, Rosalinda Di Gerlando, Luca Diamanti, Susanna Zucca, Matteo Bordoni, Orietta Pansarasa, Stella Gagliardi\",\"doi\":\"10.1002/jgm.3711\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>To investigate the expression of coding and long non-coding RNAs in LCLs, a transcriptomic profiling of sporadic ALS (SALS) and mutated patients (<i>FUS</i>, <i>TARDBP</i>, <i>C9ORF72</i> and <i>SOD1</i>) 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>We conclude that LCLs are a good model for the study of RNA deregulation in ALS.</p>\\n </section>\\n </div>\",\"PeriodicalId\":56122,\"journal\":{\"name\":\"Journal of Gene Medicine\",\"volume\":\"26 7\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-07-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3711\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gene Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3711\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gene Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3711","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
RNA expression profiling in lymphoblastoid cell lines from mutated and non-mutated amyotrophic lateral sclerosis patients
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.
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.
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