期刊
CELL STEM CELL
卷 29, 期 2, 页码 209-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2021.11.012
关键词
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资金
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/P009506/1]
- Medical Research Council (MRC), UK [MR/N000080/1, MR/N020294/1]
- BBSRC [BB/S017593/1]
- MRC Metabolic Diseases Unit [MC_UU_00014/1]
- MRC [MC_UU_ 00014/5]
- Wellcome Trust [208363/Z/17/Z]
- Cancer Research UK Cambridge Institute Genomics Core
- BBSRC [BB/S017593/1, BB/P009506/1] Funding Source: UKRI
- MRC [MR/N000080/1, MR/N020294/1] Funding Source: UKRI
Human embryonic transcription initiates at the one-cell stage, sooner than previously thought, with both upregulation and downregulation of genes impacting early development processes.
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.
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