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