Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest
© 2024. The Author(s), under exclusive licence to Springer Nature Limited..
Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Nature cell biology - 26(2024), 2 vom: 19. Feb., Seite 263-277 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Teng [VerfasserIn] |
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| Anmerkungen: |
Date Completed 16.02.2024 Date Revised 18.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41556-023-01328-0 |
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| 520 | |a Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation | ||
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| 700 | 1 | |a Hua, Rui |e verfasserin |4 aut | |
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| 700 | 1 | |a Wang, Longfei |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhang, Weiqing |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Xiangjin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lin |e verfasserin |4 aut | |
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