Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood: a Pilot RNA-seq Study

Cheryl Dykstra-Aiello, Glen C. Jickling, Bradley Ander, Xinhua Zhan, Da Liu, Heather Hull, Miles Orantia, Carolyn Ho, Boryana Stamova

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)284-289
Number of pages6
JournalTranslational Stroke Research
Volume6
Issue number4
DOIs
StatePublished - May 22 2015

Keywords

  • Alternative splicing
  • Biomarkers
  • Exon
  • Intracerebral hemorrhage
  • Ischemic stroke
  • RNA-seq

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

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