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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00814

Transcriptome Sequencing Unravels Potential Biomarkers at Different Stages of Cerebral Ischemic Stroke

 Lei Pei1*, You Cai1, Yufen Zhang2, Xiao Ke2, Yu Guo3, Chengye Yao4, Na Tang5, Pei Pang1, Gangcai Xie6, Li Fang7, Zhe Zhang2, Jincheng Li2, Yixian Fan2, Ximiao He2 and Youming Lu2*
  • 1Tongji Medical College, Huazhong University of Science and Technology, China
  • 2Huazhong University of Science and Technology, China
  • 3Wuhan Children's Hospital, China
  • 4Wuhan Union Hospital, China
  • 5Hubei Maternal and Child Health Hospital, China
  • 6Nantong University, China
  • 7Children's Hospital of Philadelphia, United States

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 day 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 day 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.

Keywords: ischemic stroke, RNA- sequencing, Small RNA-sequencing, miRNA, biomarker

Received: 25 May 2019; Accepted: 06 Aug 2019.

Copyright: © 2019 Pei, Cai, Zhang, Ke, Guo, Yao, Tang, Pang, Xie, Fang, Zhang, Li, Fan, He and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Lei Pei, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China, peilei@hust.edu.cn
Mx. Youming Lu, Huazhong University of Science and Technology, Wuhan, 430074, Hubei Province, China, lym@hust.edu.cn