Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood: a Pilot RNA-seq Study.
Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood: a Pilot RNA-seq Study.
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DOI：
10.1007/s12975-015-0407-9
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发表时间：
2015-08
影响因子：
6.9
通讯作者：
Stamova, Boryana
中科院分区：
文献类型：
--
作者：
Dykstra-Aiello, Cheryl;Jickling, Glen C.;Ander, Bradley P.;Zhan, Xinhua;Liu, DaZhi;Hull, Heather;Orantia, Miles;Ho, Carolyn;Stamova, Boryana
全转录组研究使用3′-偏倚表达微阵列研究中风患者血液中调控的基因。然而，选择性剪接的信使RNA亚型尚未在动物或人类中研究缺血性卒中或脑出血（ICH）。选择性剪接是单个基因的外显子的不同组合产生不同的mRNA和蛋白质同种型的机制。在这里，我们使用RNA测序（RNA-seq）来确定与对照组相比，ICH和心源性栓塞、大血管和腔隙性缺血性卒中的原因是否存在选择性剪接差异。使用Illumina合成测序技术将来自20个全血样品的RNA文库测序至200 M 2 × 100 bp读段。使用单因素方差分析（ANOVA）评估差异选择性剪接，并计算差异外显子使用。412个基因在各组中显示出差异性选择性剪接（假发现率，FDR; p < 0.05）。它们参与细胞免疫应答、细胞死亡和细胞存活途径。基于使用308个外显子（292个基因）的不同表达特征区分了各组（p < 0.0005;倍数变化>| 1.2|).这项初步研究表明，来自全血的选择性剪接基因在ICH中与缺血性卒中不同，并且在不同的缺血性卒中病因中也不同。这些结果需要在单独的队列中进行验证。本文的在线版本（doi：10.1007/s12975-015-0407-9）包含补充材料，可供授权用户使用。
Whole transcriptome studies have used 3′-biased expression microarrays to study genes regulated in the blood of stroke patients. However, alternatively spliced messenger RNA isoforms have not been investigated for ischemic stroke or intracerebral hemorrhage (ICH) in animals or humans. Alternative splicing is the mechanism whereby different combinations of exons of a single gene produce distinct mRNA and protein isoforms. Here, we used RNA sequencing (RNA-seq) to determine if alternative splicing differs for ICH and cardioembolic, large vessel and lacunar causes of ischemic stroke compared to controls. RNA libraries from 20 whole blood samples were sequenced to 200 M 2 × 100 bp reads using Illumina sequencing-by-synthesis technology. Differential alternative splicing was assessed using one-way analysis of variance (ANOVA), and differential exon usage was calculated. Four hundred twelve genes displayed differential alternative splicing among the groups (false discovery rate, FDR; p < 0.05). They were involved in cellular immune response, cell death, and cell survival pathways. Distinct expression signatures based on usage of 308 exons (292 genes) differentiated the groups (p < 0.0005; fold change >|1.2|). This pilot study demonstrates that alternatively spliced genes from whole blood differ in ICH compared to ischemic stroke and differ between different ischemic stroke etiologies. These results require validation in a separate cohort. The online version of this article (doi:10.1007/s12975-015-0407-9) contains supplementary material, which is available to authorized users.
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影响因子：
8.3
作者：
Sharp FR;Jickling GC
通讯作者：
Jickling GC
影响因子：
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Jickling, Glen C.;Stamova, Boryana;Ander, Bradley P.;Zhan, Xinhua;Tian, Yingfang;Liu, Dazhi;Xu, Huichun;Johnston, S. Claiborne;Verro, Piero;Sharp, Frank R.
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作者：
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通讯作者：
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影响因子：
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作者：
Jickling, Glen C.;Ander, Bradley P.;Stamova, Boryana;Zhan, Xinhua;Liu, Dazhi;Rothstein, Lena;Verro, Piero;Khoury, Jane;Jauch, Edward C.;Pancioli, Arthur M.;Broderick, Joseph P.;Sharp, Frank R.
通讯作者：
Sharp, Frank R.