Data_Sheet_9_Dynamic Alternative Splicing During Mouse Preimplantation Embryo Development.PDF

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.

可变前体mRNA剪接（alternative pre-mRNA splicing, AS）在植入前发育过程中的作用机制目前尚未完全阐明。为捕捉胚胎发生过程中可变剪接的动态变化，我们基于小鼠植入前发育时序的单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）数据开展了生物信息学分析。我们在特定发育阶段检测到大量此前未被报道的差异表达基因，并解析了小合子基因组激活与大合子基因组激活（zygotic genome activation, ZGA）两个阶段的可变剪接特征。我们构建了覆盖植入前发育全过程的可变剪接及差异可变剪接图谱。差异可变剪接基因（differentially alternatively spliced genes, DASGs）可能是植入前发育过程中的关键剪接因子（splicing factors, SFs）。此外，我们证实存在可变剪接事件的调控级联：部分关键剪接因子可通过自身转录本的差异可变剪接受到调控。我们在植入前发育过程中检测到212例异构体转换（isoform switches, ISs），其可能对解析早期胚胎发生机制至关重要。尤为重要的是，我们发现合子可变剪接激活（zygotic AS activation, ZASA）与合子基因组激活（ZGA）时序一致，并揭示植入前发育过程中可变剪接与转录过程存在偶联。本研究结果可为深入解析早期胚胎发生的调控机制提供新的视角。