Mouse and human embryonic genome activation initiate at the one-cell stage.
Level 5 - mechanism / opinion, no new human data
Bench in vitro and animal model transcriptomic study (non-clinical)
PubMed 40809689 · doi:10.3389/fcell.2025.1594995
What was done
Time-course single-cell RNA-sequencing (scRNA-seq) was conducted on one-cell mouse and healthy human embryos to profile early transcriptional activity after fertilization. In mouse one-cell embryos, functional disruption of candidate transcription factors (including MYC/c-Myc) was performed to test their requirement for embryonic development and immediate embryonic genome activation (iEGA).
What was found
In mouse embryos, iEGA initiated within 4 hours of fertilization primarily from the maternal genome, with paternal transcription appearing at approximately 10 hours. Healthy human one-cell embryos also showed significant low-magnitude transcriptional upregulation. In both species, early transcripts were canonically spliced. Inhibiting c-Myc in mouse embryos caused acute developmental arrest, disrupted iEGA, and caused the upregulation of hundreds of normally repressed genes. Specific numerical transcript counts, sample sizes, and effect sizes were not provided in the abstract.
Why it matters
These findings challenge the consensus that embryonic genome activation begins at the 2-cell stage in mice and the 4-to-8-cell stage in humans. Demonstrating transcription and active genome repression at the one-cell stage alters basic understanding of early mammalian development, epigenetic reprogramming, and embryonic arrest.
Limits
The abstract does not disclose sample sizes (n) for either mouse or human embryos, nor does it report exact statistical metrics, effect sizes, or confidence intervals. Functional inhibition experiments were conducted only in mouse embryos, leaving direct functional causality in human one-cell embryos unverified.
Cited by
- contradicts The male genome does not activate until day three after fertilization, meaning embryo development during the initial days is entirely controlled by maternal factors.