Li Feng, Xiao Yun, Huang Fei, Deng Wei, Zhao Hongying, Shi Xinrui, Wang Shuyuan, Yu Xuexin, Zhang Lianfeng, Han Zujing, Luo Longhai, Zhu Qianhua, Jiang Wei, Cheng Shujun, Li Xia, Zhang Kaitai
College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, China.
BGI Tech Solutions Co., Ltd., Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
Mol Biosyst. 2015 Dec;11(12):3253-63. doi: 10.1039/c5mb00474h.
Genome-wide expression profiling during development provides useful information to uncover the potential molecular mechanisms of development in mammals. Recent studies have revealed that a subset of lncRNAs can regulate major biological processes during development. Here, we sequenced four tissues, including brain, colon, liver and lung, using RNA-seq across three developmental stages (early, middle and late stage), and then constructed genome-wide expression profiles during macaque development. In each tissue, we identified developmental time-specific lncRNA and mRNA clusters that displayed diverse expression alteration patterns, including a gradual increase, a gradual decrease, or a reversal of expression. These lncRNAs showed more specific functional associations with their corresponding tissues relative to the developmental time-specific mRNAs. Furthermore, we identified 20 spatiotemporal-specific co-modules including 101 lncRNAs and 609 mRNAs distributed at different developmental stages in different tissues. Our findings suggested that lncRNAs could play critical roles in the development of macaques through close cooperation with mRNAs. Finally, we predicted the functions of the spatiotemporal-specific lncRNAs by their spatiotemporal cooperation with mRNAs and further validated our findings using gene knockdown data of mouse. Our study reveals the spatiotemporal characteristics of lncRNAs and provides a functional map of the spatiotemporal-specific lncRNAs during the development of macaques.
发育过程中的全基因组表达谱分析为揭示哺乳动物发育的潜在分子机制提供了有用信息。最近的研究表明,一部分长链非编码RNA(lncRNA)可以在发育过程中调节主要生物学过程。在此,我们使用RNA测序技术对猕猴发育的三个阶段(早期、中期和晚期)的脑、结肠、肝脏和肺这四种组织进行了测序,然后构建了猕猴发育过程中的全基因组表达谱。在每个组织中,我们鉴定出了发育时间特异性的lncRNA和mRNA簇,它们呈现出不同的表达变化模式,包括逐渐增加、逐渐减少或表达逆转。相对于发育时间特异性的mRNA,这些lncRNA与其相应组织表现出更特异的功能关联。此外,我们鉴定出了20个时空特异性共模块,包括分布在不同组织不同发育阶段的101个lncRNA和609个mRNA。我们的研究结果表明,lncRNA可能通过与mRNA的密切合作在猕猴发育中发挥关键作用。最后,我们通过lncRNA与mRNA的时空合作预测了时空特异性lncRNA的功能,并使用小鼠基因敲低数据进一步验证了我们的研究结果。我们的研究揭示了lncRNA的时空特征,并提供了猕猴发育过程中时空特异性lncRNA的功能图谱。