Human embryonic genome activation initiates at the one-cell stage

被引:98
作者
Asami, Maki [1 ]
Lam, Brian Y. H. [2 ]
Ma, Marcella K. [2 ]
Rainbow, Kara [2 ]
Braun, Stefanie [3 ]
VerMilyea, Matthew D. [3 ]
Yeo, Giles S. H. [2 ]
Perry, Anthony C. F. [1 ]
机构
[1] Univ Bath, Dept Biol & Biochem, Lab Mammalian Mol Embryol, Bath BA2 7AY, Avon, England
[2] Univ Cambridge, Addenbrookes Hosp, Wellcome MRC Inst Metab Sci, MRC Metab Dis Unit, Cambridge CB2 0QQ, England
[3] Ovat Fertil Austin, Embryol & Androl Labs, Austin, TX 78731 USA
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
MATERNAL MESSENGER-RNA; GENE-EXPRESSION; PREIMPLANTATION DEVELOPMENT; HUMAN OOCYTES; MOUSE; CLEAVAGE; TRANSCRIPTOME; PHOSPHORYLATION; PROLIFERATION; FERTILIZATION;
D O I
10.1016/j.stem.2021.11.012
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:209 / +
页数:13
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