Human embryonic genome activation initiates at the one-cell stage

Maki Asami, Brian Y H Lam, Marcella K Ma, Kara Rainbow, Stefanie Braun, Matthew D VerMilyea, Giles S H Yeo, Anthony C F Perry

Research output: Contribution to journalArticlepeer-review

49 Citations (SciVal)


In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts. Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos. These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought. The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer.
Original languageEnglish
Pages (from-to)209-216.e4
JournalCell Stem Cell
Issue number2
Early online date21 Dec 2021
Publication statusPublished - 3 Feb 2022


  • embryonic genome activation (EGA)
  • fertilization
  • human one-cell embryo
  • single-cell RNA-seq
  • totipotency
  • transcriptome
  • zygote

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


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