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

Cell Stem Cell. 2019 Nov 7;25(5):697-712.e6. doi: 10.1016/j.stem.2019.09.004. Epub 2019 Oct 3.

Abstract

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.

Keywords: androgenetic embryos; biparental embryos; embryonic genome activation; maternally biased expressed genes; parent-of-origin effects; parthenogenetic embryos; paternally biased expressed genes; single-cell RNA sequencing.

MeSH terms

  • Blastocyst / metabolism*
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Protein 2 / metabolism
  • Embryo, Mammalian / metabolism*
  • Embryonic Development / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Gene Ontology
  • Homeodomain Proteins / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • Oocytes / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA-Seq
  • Repetitive Sequences, Nucleic Acid / genetics
  • Single-Cell Analysis
  • Time-Lapse Imaging
  • Transcriptome / genetics*

Substances

  • DNA-Binding Proteins
  • DUX4L1 protein, human
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Homeodomain Proteins
  • KLF3 protein, human
  • Kruppel-Like Transcription Factors
  • RNA, Long Noncoding
  • ZNF263 protein, human