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

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 -res-olution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a pro-gram 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 dis-rupts 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.

Automated summary

Using high-resolution single-cell RNA sequencing, we investigated the transcriptional process during early embryonic development. Our findings suggest that embryonic gene expression initiates within 4 hours of fertilization, primarily from the maternal genome, and is downregulated at the two-cell stage. These insights shed light on the intracellular mechanisms regulating mammalian development and have implications for cancer research.