Single-cell multiomics sequencing reveals the functional regulatory landscape of early embryos

Yang Wang, Peng Yuan, Zhiqiang Yan, Ming Yang, Ying Huo, Yanli Nie, Xiaohui Zhu, Jie Qiao () and Liying Yan ()
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Yang Wang: Peking University Third Hospital
Peng Yuan: Peking University Third Hospital
Zhiqiang Yan: Peking University Third Hospital
Ming Yang: Peking University Third Hospital
Ying Huo: Peking University Third Hospital
Yanli Nie: Peking University Third Hospital
Xiaohui Zhu: Peking University Third Hospital
Jie Qiao: Peking University Third Hospital
Liying Yan: Peking University Third Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Extensive epigenetic reprogramming occurs during preimplantation embryo development. However, it remains largely unclear how the drastic epigenetic reprogramming contributes to transcriptional regulatory network during this period. Here, we develop a single-cell multiomics sequencing technology (scNOMeRe-seq) that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in the same individual cell. We apply this method to depict a single-cell multiomics map of mouse preimplantation development. We find that genome-wide DNA methylation remodeling facilitates the reconstruction of genetic lineages in early embryos. Further, we construct a zygotic genome activation (ZGA)-associated regulatory network and reveal coordination among multiple epigenetic layers, transcription factors and repeat elements that instruct proper ZGA. Cell fates associated cis-regulatory elements are activated stepwise in post-ZGA stages. Trophectoderm (TE)-specific transcription factors play dual roles in promoting the TE program while repressing the inner cell mass (ICM) program during the ICM/TE separation.

Date: 2021
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DOI: 10.1038/s41467-021-21409-8

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