Zhang Guilong, Chen Lukui, Guo Xiaoyuan, Wang Hong, Chen Wanghao, Wu Guojian, Gu Bin, Miao Wei, Kong Jun, Jin Xingxing, Yi Guoqing, You Yang, Su Xinhui, Gu Ning
J Biomed Nanotechnol. 2018 Jun 1;14(6):1075-1089. doi: 10.1166/jbn.2018.2567.
Stroke recovery is associated with neural stem cell (NSC) development and neurovascular unit reconstruction. The exosome, as an important intercellular player in neurovascular communication, mediates neuro-restorative events by transferring exosomal protein and RNA cargoes. In this study, we explored the role of exosomal microRNAs (miRNAs) in human NSCs (hNSCs), and analyzed the expression profiles of miRNAs in hNSC-derived and hypoxic preconditioning hNSC-derived exosomes with the help of next generation sequencing (NGS). The results demonstrated that a certain proportion of miRNAs were differentially expressed in both exosomes. In addition, target gene prediction and Gene Ontology (GO) enrichment analysis showed that these genes were associated with differential miRNAs primarily participating in biological processes (regulation of cellular process), cellular component (intracellular membrane-bounded organelle), and molecular function (binding). Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway enrichment data suggested that most of targeted genes involved in PI3K-Akt, Hippo, MAPK, mTOR, and Endocytosis etc. signaling pathways. We identified the interesting and important expressed miRNA and considered that miR-98-3p might be a special hNSC-derived exosomal-miRNA which was significantly downregulated under hypoxic preconditioning. The hNSCs-derived exosomes were capable of modulating gene expression or promoting stroke therapy. We observed that after hypoxic preconditioning, the functions of these exosomes were changed, and exosomal-miRNAs expression profile was different. In summary, our study suggested that hNSC-derived exosomal miRNAs including hypoxic preconditioning exosomal miRNAs provided a new strategy for the diagnosis and treatment of stroke patients.
中风恢复与神经干细胞（NSC）发育和神经血管单元重建相关。外泌体作为神经血管通讯中重要的细胞间参与者，通过转运外泌体蛋白和RNA货物介导神经修复事件。在本研究中，我们探讨了外泌体微小RNA（miRNA）在人神经干细胞（hNSC）中的作用，并借助下一代测序（NGS）分析了hNSC来源和缺氧预处理hNSC来源的外泌体中miRNA的表达谱。结果表明，一定比例的miRNA在两种外泌体中均有差异表达。此外，靶基因预测和基因本体（GO）富集分析表明，这些基因与主要参与生物过程（细胞过程调控）、细胞成分（细胞内膜结合细胞器）和分子功能（结合）的差异miRNA相关。京都基因与基因组百科全书通路（KEGG）富集数据表明，大多数靶基因参与PI3K-Akt、Hippo、MAPK、mTOR和内吞作用等信号通路。我们鉴定出了有趣且重要的表达miRNA，并认为miR-98-3p可能是一种特殊的hNSC来源的外泌体miRNA，在缺氧预处理下显著下调。hNSC来源的外泌体能够调节基因表达或促进中风治疗。我们观察到，缺氧预处理后，这些外泌体的功能发生了变化，外泌体miRNA表达谱也不同。总之，我们的研究表明，hNSC来源的外泌体miRNA，包括缺氧预处理外泌体miRNA，为中风患者的诊断和治疗提供了一种新策略。
