Human embryonic genome activation initiates at the one-cell stage

Cell Stem Cell. 2022 Feb 3;29(2):209-216.e4. doi: 10.1016/j.stem.2021.11.012. Epub 2021 Dec 21.


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.

Keywords: embryonic genome activation (EGA); fertilization; human one-cell embryo; single-cell RNA-seq; totipotency; transcriptome; zygote.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blastocyst
  • Embryo, Mammalian* / metabolism
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental
  • Genome, Human*
  • Humans
  • Oocytes