Laboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia.
Int J Mol Sci. 2023 May 27;24(11):9361. doi: 10.3390/ijms24119361.
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) whose aetiology is only partly understood. Investigating the intricate transcriptional changes occurring in MS brains is critical to unravel novel pathogenic mechanisms and therapeutic targets. Unfortunately, this process is often hindered by the difficulty in retrieving an adequate number of samples. However, by merging data from publicly available datasets, it is possible to identify alterations in gene expression profiles and regulatory pathways that were previously overlooked. Here, we merged microarray gene expression profiles obtained from CNS white matter samples taken from MS donors to identify novel differentially expressed genes (DEGs) linked with MS. Data from three independent datasets (GSE38010, GSE32915, and GSE108000) were combined and used to detect novel DEGs using the Stouffer's Z-score method. Corresponding regulatory pathways were analysed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. Finally, top up- and down-regulated transcripts were validated by real-time quantitative PCR (qPCR) using an independent set of white matter tissue samples obtained from MS donors with different disease subtypes. There were a total of 1446 DEGs, of which 742 were up-regulated and 704 genes were down-regulated. DEGs were associated with several myelin-related pathways and protein metabolism pathways. Validation studies of selected top up- or down-regulated genes highlighted MS subtype-specific differences in the expression of some of the identified genes, underlining a more complex scenario of white matter pathology amongst people afflicted by this devastating disease.
多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性疾病，其病因尚不完全清楚。研究 MS 大脑中发生的复杂转录变化对于揭示新的发病机制和治疗靶点至关重要。不幸的是，这个过程通常受到难以获得足够数量的样本的阻碍。然而，通过合并来自公开数据集的数据，可以识别以前被忽视的基因表达谱和调控途径的改变。在这里，我们合并了从 MS 供体的中枢神经系统白质样本中获得的微阵列基因表达谱，以鉴定与 MS 相关的新的差异表达基因（DEGs）。合并了来自三个独立数据集（GSE38010、GSE32915 和 GSE108000）的数据，并使用 Stouffer's Z 分数方法来检测新的 DEGs。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径数据库分析相应的调控途径。最后，通过使用来自 MS 供体不同疾病亚型的独立白质组织样本进行实时定量 PCR（qPCR）验证了上调和下调的转录本。共有 1446 个 DEGs，其中 742 个上调，704 个下调。DEGs 与几种髓鞘相关途径和蛋白质代谢途径有关。对选定的上调或下调基因的验证研究突出了一些鉴定基因在 MS 亚型表达中的差异，强调了在受这种破坏性疾病影响的人群中，白质病理学的情况更为复杂。
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