Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development

To investigate the contribution of parental genomes to early embryogenesis, we profiled the single-cell transcriptomes of human biparental and uniparental embryos systematically from the 1-cell to the morula stage. We observed that uniparental embryos exhibited variable and decreased embryonic genome activation (EGA). Comparative transcriptome analysis identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs) in the preimplantation stages. MBGs became apparent at the 4-cell stage and contributed to the initiation of EGA, whereas PBGs preferentially appeared at the 8-cell stage and might affect embryo compaction and trophectoderm specification. Regulatory network analysis revealed that DUX4, EGR2, and DUXA are key transcription factors in MBGs’ expression; ZNF263 and KLF3 are important for PBGs’ expression. We demonstrated that parent-specific DNA methylation might account for the expression of most PBGs. Our results provide a valuable resource to understand parental genome activation and might help to elucidate parent-of-origin effects in early human development. [Display omitted] •scRNA-seq of human biparental and uniparental embryos revealed parent-of-origin effects•1,388 MBGs and PBGs are involved in initiation of EGA and early differentiation•Transcriptional regulatory networks uncovered key transcription factors for MBGs and PBGs•WGBS demonstrated parent-specific DNA methylation pattern in early embryos Leng et al. performed a comprehensive survey of transcriptional activities between biparental and uniparental embryos by single-cell RNA sequencing. They provide insights into the critical features of parental genome activation before implantation and help elucidate parent-of-origin effects in early human development.