Rodrigues Aline Beatriz Mello, Passetti Fabio, Guimarães Ana Carolina Ramos
Laboratory for Applied Genomics and Bioinnovations, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, RJ, Brazil.
Instituto Carlos Chagas - Fiocruz/Paraná, Curitiba, PR, Brazil.
Neuroinformatics. 2025 Jan 21;23(2):10. doi: 10.1007/s12021-024-09713-2.
Multiple sclerosis (MS) is a neurological disease causing myelin and axon damage through inflammatory and autoimmune processes. Despite affecting millions worldwide, understanding its genetic pathways remains limited. The choroid plexus (ChP) has been studied in neurodegenerative processes and diseases like MS due to its dysregulation, yet its role in MS pathophysiology remains unclear. Our work re-evaluates the ChP transcriptome in progressive MS patients and compares gene expression profiles using diverse methodological strategies. Samples from patient and healthy control RNASeq sequencing of brain tissue from post-mortem patients (GEO: GSE137619) were used. After an evaluation and quality control of these data, they had their transcripts mapped and quantified against the reference transcriptome GRCh38/hg38 of Homo sapiens using three strategies to identify differentially expressed genes in progressive MS patients. Functional analysis of genes revealed their involvement in immune processes, cell adhesion and migration, hormonal actions, amino acid transport, chemokines, metals, and signaling pathways. Our findings can offer valuable insights for progressive MS therapies, suggesting specific genes influence immune cell recruitment and potential ChP microenvironment changes. Combining complementary approaches maximizes literature coverage, facilitating a deeper understanding of the biological context in progressive MS.
多发性硬化症（MS）是一种通过炎症和自身免疫过程导致髓鞘和轴突损伤的神经疾病。尽管全球有数百万人受其影响，但对其遗传途径的了解仍然有限。由于脉络丛（ChP）失调，它已在神经退行性过程和诸如MS等疾病中得到研究，但其在MS病理生理学中的作用仍不清楚。我们的工作重新评估了进展型MS患者的脉络丛转录组，并使用多种方法策略比较基因表达谱。使用了来自患者和健康对照的死后患者脑组织RNA测序样本（GEO：GSE137619）。在对这些数据进行评估和质量控制后，使用三种策略将它们的转录本与智人的参考转录组GRCh38/hg38进行比对和定量，以鉴定进展型MS患者中差异表达的基因。对基因的功能分析揭示了它们参与免疫过程、细胞黏附和迁移、激素作用、氨基酸转运、趋化因子、金属和信号通路。我们的发现可为进展型MS治疗提供有价值的见解，表明特定基因影响免疫细胞募集和脉络丛潜在的微环境变化。结合互补方法可最大限度地扩大文献覆盖范围，有助于更深入地了解进展型MS的生物学背景。
