Human embryonic genome activation initiates at the one-cell stage.

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Asami, Maki 
Lam, Brian YH 
Ma, Marcella K 
Rainbow, Kara 
Braun, Stefanie 

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 upregulation 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.

embryonic genome activation (EGA), fertilization, human one-cell embryo, single-cell RNA-seq, totipotency, transcriptome, zygote, Blastocyst, Embryo, Mammalian, Embryonic Development, Gene Expression Regulation, Developmental, Genome, Human, Humans, Oocytes
Journal Title
Cell Stem Cell
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Elsevier BV
Wellcome Trust (208363/Z/17/Z)
Biotechnology and Biological Sciences Research Council (BB/S017593/1)
MRC (MC_UU_00014/1)
MRC (MC_UU_00014/5)
Medical Research Council (MC_UU_12012/5)
MRC (MR/S026193/1)
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