HUMAN AND MOUSE EMBRYONIC GENOME ACTIVATION INITIATES AT THE ONE-CELL STAGE

In fertilization, the gametes, sperm and oocyte, combine to produce a totipotent one-cell embryo. At this point, their genomes are silent, so transcription must be activated in the new embryo, a process termed embryonic genome activation (EGA). EGA is a critical developmental event, yet its timing and profile remain elusive in both human and mouse.
The prevailing view is that EGA occurs by the eight-cell stage in human embryos, and the late one-cell stage in mouse embryos, but this leaves multiple issues unresolved. We report high resolution single-cell RNA sequencing (scRNA-seq) following polyadenylation-independent library preparation in mouse and human one-cell embryos.
Results showed that human gene expression initiates at the one-cell stage and is disrupted in morphologically abnormal embryos. The mouse transcriptome profile revealed analogously low-amplitude gene expression that initiated as a program within four hours of sperm-egg union. We refer to the first 12 hours of gene expression as immediate EGA, iEGA. In both human and mouse, transcripts were canonically spliced and down-regulated coincident with ‘major’ EGA at the two-cell stage. Bioinformatic analyses identified experimentally verified upstream regulators including MYC.