Abstract
SummaryIn 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.
Highlights
Fertilizing spermatozoa and metaphase II oocytes are transcriptionally quiescent (Zhou and Dean, 2015)
Whole-transcriptome amplification produced indistinguishable yields between oocytes and one-cell embryos (p = 0.595), and indepth scRNA-seq yielded a mean of 66.3 million reads per cell
The number of differentially expressed genes (DEGs) inversely correlated with fold-change (FC, log2FC; Figure S1B), and there were 1,395 DEGs with an absolute log2FC
Summary
Fertilizing spermatozoa and metaphase II (mII) oocytes are transcriptionally quiescent (Zhou and Dean, 2015). The first transcription in newly formed embryos is known as embryonic genome activation (EGA), but its onset, timing, and profile are poorly understood (Jukam et al, 2017). EGA is held to have occurred by the eight-cell stage, up to $68 h ($3 days) after fertilization (Braude et al, 1988; Leng et al, 2019; Tesarık et al, 1988; Vassena et al, 2011; Xue et al, 2013; Yan et al, 2013), but this model is likely incomplete. The model does not explain how the embryo genome is maintained in a transcriptionally silent state during cell proliferation to the eight-cell stage (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). We evaluated the open possibility that gene expression is triggered after fertilization in human onecell embryos
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