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

Nat Commun. 2021 Feb 23;12(1):1247. doi: 10.1038/s41467-021-21409-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Blastocyst / metabolism*
  • Cell Lineage / genetics
  • Chromatin / metabolism
  • DNA Methylation / genetics
  • Ectoderm / cytology
  • Embryo, Mammalian / metabolism*
  • Female
  • Gene Expression Regulation, Developmental*
  • Genomics*
  • Male
  • Mice
  • Phylogeny
  • Promoter Regions, Genetic
  • Single-Cell Analysis*
  • Zygote / metabolism

Substances

  • Chromatin