Human embryonic genome activation initiates at the one-cell stage.
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Authors
Asami, Maki
Lam, Brian YH
Ma, Marcella K
Rainbow, Kara
Braun, Stefanie
VerMilyea, Matthew D
Yeo, Giles SH
Perry, Anthony CF
Publication Date
2022-02-03Journal Title
Cell Stem Cell
ISSN
1934-5909
Publisher
Elsevier BV
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Asami, M., Lam, B. Y., Ma, M. K., Rainbow, K., Braun, S., VerMilyea, M. D., Yeo, G. S., & et al. (2022). Human embryonic genome activation initiates at the one-cell stage.. Cell Stem Cell https://doi.org/10.1016/j.stem.2021.11.012
Abstract
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.
Relationships
Is supplemented by: https://doi.org/10.17863/CAM.78715
Sponsorship
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)
Identifiers
External DOI: https://doi.org/10.1016/j.stem.2021.11.012
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331281
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