Human Embryonic Genome Activation Initiates at the One-cell Stage

Presented at: Published in Cell Stem Cell

Authors: Maki Asami, Brian Y.H. Lam, Marcella K. Ma, Matthew D. VerMilyea, Giles S.H. Yeo, Anthony C.F. Perry

SUMMARY
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 up-regulation 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.

Maki Asami,1,4 Brian Y.H. Lam,2,4 Marcella K. Ma,2 Kara Rainbow,2 Stefanie Braun,3 Matthew D. VerMilyea,3, *Giles S.H. Yeo,2, * and Anthony C.F. Perry1,5, Q1 * 1 Q9 Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, England 2MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, 3Ovation Fertility Austin, Embryology and Andrology Laboratories, Austin, TX 78731, USA
4These authors contributed equally
5Lead contact