Transcriptome Sequencing Unravels Potential Biomarkers at Different Stages of Cerebral Ischemic Stroke
Transcriptome Sequencing Unravels Potential Biomarkers at Different Stages of Cerebral Ischemic Stroke
复制标题
转录组测序揭示了脑缺血性中风不同阶段的潜在生物标志物
DOI：
10.3389/fgene.2019.00814
复制
发表时间：
2019-09-24
影响因子：
3.7
通讯作者：
Lu, Youming
中科院分区：
文献类型：
--
作者：
Cai, You;Zhang, Yufen;Lu, Youming
缺血性卒中占所有卒中的87%，是中国发病率和死亡率的主要原因。虽然中风的遗传学和表观遗传学已被广泛研究，但很少有研究探讨它们在中风不同阶段的关系。本研究采用小鼠短暂性大脑中动脉闭塞（tMCAO）模型和生物信息学分析评估缺血性卒中不同阶段转录组变化的特征。在第1、3、7、14和28天从tMCAO小鼠中取出大脑皮质组织用于RNA-Seq和小RNA-Seq文库构建、测序和生物信息学分析。我们鉴定了差异表达（DE）基因和miRNA，并揭示了在每个时间点上调或下调的DEmiRNA与相应改变的DE基因靶点的关联。此外，不同的生物学途径在不同的时间点被激活;因此，验证了三组miRNA可能代表缺血性卒中后第1、3和7天的潜在临床生物标志物。值得注意的是，这代表了这些miRNA中的一些与中风的第一个功能关联，例如，miR-2137、miR-874-5p和miR-5099。总之，我们的研究结果为从单点、单药卒中治疗方法向多时间点多药联合治疗过渡奠定了基础。
Ischemic stroke, which accounts for 87% of all strokes, constitutes the leading cause of morbidity and mortality in China. Although the genetics and epigenetics of stroke have been extensively investigated, few studies have examined their relationships at different stages of stroke. This study assessed the characteristics of transcriptome changes at different stages of ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO) and bioinformatics analyses. Cerebral cortex tissues from tMCAO mice at days 1, 3, 7, 14, and 28 were removed for RNA-Seq and small RNA-Seq library construction, sequencing, and bioinformatics analysis. We identified differentially expressed (DE) genes and miRNAs and revealed an association of the up-regulated or down-regulated DEmiRNAs with the correspondingly altered DEgene targets at each time point. In addition, different biological pathways were activated at different time points; thus, three groups of miRNAs were verified that may represent potential clinical biomarkers corresponding to days 1, 3, and 7 after ischemic stroke. Notably, this represents the first functional association of some of these miRNAs with stroke, e.g., miR-2137, miR-874-5p, and miR-5099. Together, our findings lay the foundation for the transition from a single-point, single-drug stroke treatment approach to multiple-time-point multi-drug combination therapies.