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

• Published in: Nature communications Vol. 12; no. 1; pp. 1247 - 14
• Main Authors: Wang, Yang, Yuan, Peng, Yan, Zhiqiang, Yang, Ming, Huo, Ying, Nie, Yanli, Zhu, Xiaohui, Qiao, Jie, Yan, Liying
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38/23; 38/39; 45/91; 631/136/1455; 631/1647/2210/2211; 631/1647/2210/2213; 631/337/100; 631/337/176/1988; 64/60; Accessibility; Alleles; Animals; Blastocyst - metabolism; Cell Lineage - genetics; Chromatin; Chromatin - metabolism; Deoxyribonucleic acid; Developmental stages; DNA; DNA methylation; DNA Methylation - genetics; DNA sequencing; Ectoderm - cytology; Embryo, Mammalian - metabolism; Embryos; Epigenetics; Female; Gene expression; Gene Expression Regulation, Developmental; Genomes; Genomics; Humanities and Social Sciences; Male; Mice; multidisciplinary; Phylogeny; Promoter Regions, Genetic; Regulatory sequences; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Single-Cell Analysis; Transcription factors; Trophectoderm; Zygote - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21409-8

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. Extensive epigenetic reprogramming occurs during preimplantation embryo development. Here the authors develop a single cell multiomics sequencing technology that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in the same individual cell and apply this method to study mouse preimplantation embryos.