蛛网膜下腔出血或假手术 72 小时后小鼠大脑小胶质细胞中不同表达的 RNA 结合蛋白基因分析。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-08-02 DOI:10.1186/s12920-024-01972-x
Xinyi Pan, Hengyang Ouyang, Xue Xiao, Xiaobing Zhou, Lingfeng Lai
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引用次数: 0

摘要

背景:蛛网膜下腔出血(SAH)导致的脑损伤预后较差。先前的研究表明,RBPs 的功能异常可能参与脑损伤、神经炎症并进一步影响小胶质细胞的稳态。然而,还没有研究系统地分析了 SAH 期间小胶质细胞中 RBPs 基因的全基因组异常表达:方法:从 GEO 数据库 GSE167957 中下载 SAH 小鼠组(SAH)和假手术对照组(sham)小胶质细胞的 RNA-seq 数据,其中包括 4 个假手术组样本和 4 个 SAH 组样本,用于后续分析。利用GO和KEGG功能富集分析,我们对差异表达基因(DEGs)、替代剪接模式和共表达网络进行了全面研究,以深入了解RNA结合蛋白(RBPs)的差异表达和差异替代剪接事件(ASEs)在SAH(蛛网膜下腔出血)组和假手术组之间的差异。该分析旨在阐明SAH导致脑损伤期间小胶质细胞中RBPs异常表达的潜在机制:结果:对小胶质细胞中差异表达的 RBPs 和差异 ASEs 进行了基因表达的 ASEs 和共表达分析。GO和KEGG功能富集分析表明,异常表达的RBPs如Mcm7、Mtdh、SRSF3和Hnrnpa2b1可能通过改变剪接影响和调控下游的Csnk1d、Uckl1和其他蛋白磷酸化相关基因:结论:在本研究中,RBPs在SAH继发性脑损伤发展过程中在小胶质细胞中异常表达,调控下游基因的剪接变化,影响SAH脑损伤的进展。这意味着,RBPs 对确定 SAH 后脑损伤的新治疗靶点非常重要。
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Analysis of different expression RNA binding protein genes in mouse microglia cell from the brains of mice 72 h after subarachnoid hemorrhage or sham operation.

Background: The prognosis of brain injury caused by subarachnoid hemorrhage (SAH) is poor. Previous studies showed that abnormal function of RBPs might be involved in brain injury, neuroinflammation and further affect microglia homeostasis. However, no studies have systematically analyzed the genome-wide abnormal expression of RBPs genes in microglia during SAH.

Methods: RNA-seq data of microglia from the SAH mouse group (SAH) and control sham-operated mouse group (sham) were downloaded from the GEO database in GSE167957, including four samples from the sham group and four samples from the SAH group for subsequent analysis.Utilizing GO and KEGG functional enrichment analyses, we conducted a comprehensive study of differentially expressed genes (DEGs), alternative splicing patterns, and co-expression networks to gain deeper insights into the differential expression of RNA-binding proteins (RBPs) and differential alternative splicing events (ASEs) between the SAH (subarachnoid hemorrhage) and sham groups. This analysis aimed to elucidate the potential mechanisms underlying the aberrant expression of RBPs in microglia during brain injury caused by SAH.

Results: ASEs and co-expression analyses of differentially expressed RBPs and differential ASEs were carried out in microglia in terms of gene expression. GO and KEGG functional enrichment analysis showed that aberrantly expressed RBPs such as Mcm7, Mtdh, SRSF3, and Hnrnpa2b1 may affect and regulate downstream Csnk1d, Uckl1 and other protein phosphorylation-related genes by alterative splicing.

Conclusion: RBPs were aberrantly expressed in microglia during the development of brain injury secondary to SAH, regulating alterative splicing of downstream genes and influencing the progression of SAH brain injury in this study. This implies that RBPs are important for the identification of new therapeutic targets for brain injury after SAH.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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