Yang Qichang, Wu Jing, Zhao Jian, Xu Tianyi, Zhao Zhongming, Song Xiaofeng, Han Ping
Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, Jiangsu, China.
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
BMC Syst Biol. 2018 Dec 21;12(Suppl 8):128. doi: 10.1186/s12918-018-0651-1.
Circular RNAs (circRNAs) have recently been found to be expressed in human brain tissue, and many lines ofevidence indicate that circRNAs play regulatory roles in neurodevelopment. Proliferation and differentiation of neural stem cells (NSCs) are critical parts during development of central nervous system (CNS).To date, there have been no reports ofcircRNA expression profiles during the differentiation of mouse NSCs. We hypothesizethat circRNAs mayregulate gene expression in the proliferation anddifferentiation of NSCs.
In this study, we obtained NSCs from the wild-type C57BL/6 J mouse fetal cerebral cortex. We extracted total RNA from NSCs in different differentiation stagesand then performed RNA-seq. By analyzing the RNA-Seq data, we found 37circRNAs and 4182 mRNAs differentially expressedduringthe NSC differentiation. Gene Ontology (GO) enrichment analysis of thecognate linear genes of these circRNAsrevealed that some enriched GO terms were related to neural activity. Furthermore, we performed a co-expression network analysis of these differentially expressed circRNAs and mRNAs. The result suggested a stronger GO enrichmentin neural features for both the cognate linear genes of circRNAs and differentially expressed mRNAs.
We performed the first circRNA investigation during the differentiation of mouse NSCs. Wefound that12 circRNAs might have regulatory roles duringthe NSC differentiation, indicating that circRNAs might be modulated during NSC differentiation.Our network analysis suggested the possible complex circRNA-mRNA mechanisms during differentiation, and future experimental workis need to validate these possible mechanisms.
环状RNA（circRNAs）最近被发现在人类脑组织中表达，并且许多证据表明circRNAs在神经发育中发挥调节作用。神经干细胞（NSCs）的增殖和分化是中枢神经系统（CNS）发育过程中的关键部分。迄今为止，尚未有关于小鼠神经干细胞分化过程中circRNA表达谱的报道。我们假设circRNAs可能在神经干细胞的增殖和分化过程中调节基因表达。
在本研究中，我们从野生型C57BL/6 J小鼠胚胎大脑皮层中获得神经干细胞。我们从处于不同分化阶段的神经干细胞中提取总RNA，然后进行RNA测序。通过分析RNA测序数据，我们发现在神经干细胞分化过程中有37种circRNAs和4182种mRNA差异表达。对这些circRNAs的同源线性基因进行基因本体论（GO）富集分析，结果显示一些富集的GO术语与神经活动相关。此外，我们对这些差异表达的circRNAs和mRNAs进行了共表达网络分析。结果表明，circRNAs的同源线性基因和差异表达的mRNAs在神经特征方面的GO富集更强。
我们首次对小鼠神经干细胞分化过程中的circRNAs进行了研究。我们发现12种circRNAs可能在神经干细胞分化过程中发挥调节作用，这表明circRNAs可能在神经干细胞分化过程中受到调控。我们的网络分析表明在分化过程中可能存在复杂的circRNA-mRNA机制，未来需要进行实验工作来验证这些可能的机制。
