A program of successive gene expression in mouse one-cell embryos

Maki Asami, Brian Y. H. Lam, Martin Hoffmann, Toru Suzuki, Xin Lu, Naoko Yoshida, Marcella K Ma, Kara Rainbow, Miodrag Gužvić, Matthew D. Vermilyea, Giles S. H. Yeo, Christoph A. Klein, Anthony C. F. Perry

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At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.

Original languageEnglish
Article number112023
JournalCell Reports
Issue number2
Early online date31 Jan 2023
Publication statusPublished - 28 Feb 2023


  • CP: Developmental biology
  • EGA
  • cancer
  • embryonic genome activation
  • fertilization
  • human genome editing
  • single-cell RNA-seq
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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