Single-cell multiomics sequencing reveals the functional regulatory landscape of early embryos

Abstract Extensive epigenetic reprogramming occurs during preimplantation embryo development. However, it remains largely unclear how the drastic contributes to transcriptional regulatory network this period. Here, we develop a single-cell multiomics sequencing technology (scNOMeRe-seq) that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in same individual cell. We apply method depict map mouse find remodeling facilitates reconstruction genetic lineages early embryos. Further, construct zygotic genome activation (ZGA)-associated reveal coordination among multiple layers, transcription factors repeat elements instruct proper ZGA. Cell fates associated cis-regulatory are activated stepwise post-ZGA stages. Trophectoderm (TE)-specific play dual roles promoting TE program while repressing inner cell mass (ICM) ICM/TE separation.