Xing Yongqiang, Yang Wuritu, Liu Guoqing, Cui Xiangjun, Meng Hu, Zhao Hongyu, Zhao Xiujuan, Li Jun, Liu Zhe, Zhang Michael Q, Cai Lu
School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, Baotou, China.
Front Bioeng Biotechnol. 2020 Feb 7;8:35. doi: 10.3389/fbioe.2020.00035. eCollection 2020.
The mechanism of alternative pre-mRNA splicing (AS) during preimplantation development is largely unknown. In order to capture the dynamic changes of AS occurring during embryogenesis, we carried out bioinformatics analysis based on scRNA-seq data over the time-course preimplantation development in mouse. We detected numerous previously-unreported differentially expressed genes at specific developmental stages and investigated the nature of AS at both minor and major zygotic genome activation (ZGA). The AS and differential AS atlas over preimplantation development were established. The differentially alternatively spliced genes (DASGs) are likely to be key splicing factors (SFs) during preimplantation development. We also demonstrated that there is a regulatory cascade of AS events in which some key SFs are regulated by differentially AS of their own gene transcripts. Moreover, 212 isoform switches (ISs) during preimplantation development were detected, which may be critical for decoding the mechanism of early embryogenesis. Importantly, we uncovered that zygotic AS activation (ZASA) is in conformity with ZGA and revealed that AS is coupled with transcription during preimplantation development. Our results may provide a deeper insight into the regulation of early embryogenesis.
着床前发育过程中可变前体mRNA剪接（AS）的机制在很大程度上尚不清楚。为了捕捉胚胎发生过程中发生的AS动态变化，我们基于小鼠着床前发育时间进程的单细胞RNA测序（scRNA-seq）数据进行了生物信息学分析。我们在特定发育阶段检测到许多先前未报道的差异表达基因，并研究了在小的和大的合子基因组激活（ZGA）时AS的性质。建立了着床前发育过程中的AS和差异AS图谱。差异可变剪接基因（DASG）可能是着床前发育过程中的关键剪接因子（SF）。我们还证明了存在一个AS事件的调控级联，其中一些关键SF由其自身基因转录本的差异AS调控。此外，在着床前发育过程中检测到212个异构体转换（IS），这可能对解读早期胚胎发生机制至关重要。重要的是，我们发现合子AS激活（ZASA）与ZGA一致，并揭示了着床前发育过程中AS与转录偶联。我们的结果可能为深入了解早期胚胎发生的调控提供见解。
