Single-cell multiomics sequencing reveals the functional regulatory landscape of early embryos.
Yang WangPeng YuanZhiqiang YanMing YangYing HuoYanli NieXiaohui ZhuJie QiaoLi-Ying YanPublished in: Nature communications (2021)
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.
Keyphrases
- single cell
- dna methylation
- genome wide
- transcription factor
- rna seq
- gene expression
- high throughput
- copy number
- dna binding
- quality improvement
- stem cells
- dna damage
- cell therapy
- pregnant women
- heat shock protein
- bone marrow
- mesenchymal stem cells
- genome wide identification
- mass spectrometry
- long non coding rna
- heat shock