Abstract
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.
Highlights
Decoding molecular mechanisms of totipotency and pluripotency is crucial to the understanding of reproductive biology and to regenerative medicine (Hamatani et al, 2004)
It has been extensively studied that gene expression level is spatial-temporally dynamic during early embryonic development (Fan et al, 2015; Schultz et al, 2018)
Some evidence indicated that alternative pre-mRNA splicing (AS) could correlate closely with preimplantation development, suggesting a key role for splicing in regulating early embryonic development (Revil et al, 2010; Yan et al, 2013)
Summary
Decoding molecular mechanisms of totipotency and pluripotency is crucial to the understanding of reproductive biology and to regenerative medicine (Hamatani et al, 2004). Preimplantation process, which encompasses the period from fertilization to implantation, is a fundamental developmental stage that has been extensively studied in order to gain insight to totipotency and pluripotency (Yan et al, 2013; Petropoulos et al, 2016). Numerous scRNA-seq studies on mouse or human preimplantation embryos have identified a large number of genes and signaling. Alternative Splicing During Preimplantation Development pathways involved in early stages of embryonic development (Hamatani et al, 2004, 2006; Yan et al, 2013; Petropoulos et al, 2016). The molecular regulatory mechanisms underlying preimplantation process remain incompletely understood, especially the effect of AS in this process
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