Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Early Embryonic Development

Abstract

\n BackgroundSingle-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression. Although several studies investigated the expression profile of early embryos, they mainly focused on the expression changes at gene level. Here we systematically explored the gene expression dynamics of human early embryonic development from expression level, alternative splicing, isoform switching and expression regulatory network. ResultsWe found that the genes involved in significant changes of these three aspects are all gradually decreased along embryonic development from E3 to E7 stage. Moreover, these three types of variations are complementary for profiling expression dynamics and they vary greatly across embryonic development as well as between different sexes. Strikingly, only a small number of genes exhibited prominent expression level changes between male and female embryos in E3 stage, whereas many more genes showed variations in alternative splicing and major isoform switching. Additionally, we identified functionally important specific gene regulatory modules for each stage and revealed dynamic usage of transcription factor binding motifs (TFBMs). Conclusions\ufeffCollectively, our study gain insights into the expression dynamics of early embryonic development from expression level, alternative splicing, isoform switching and gene regulatory networks, which could benefit the understanding of underlying mechanism of embryonic development.