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Single-cell multi-omics sequencing of human early embryos.

Lin Li1,2, Fan Guo3, Yun Gao1,2

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This study maps DNA methylation and chromatin accessibility in early human embryos using single-cell sequencing. It reveals differences from mice and a feedback loop between transcription and chromatin state.

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Area of Science:

  • Epigenetics
  • Developmental Biology
  • Genomics

Background:

  • Epigenetic information, including DNA methylation and chromatin states, is crucial for early development but poorly understood in human embryos.
  • Existing knowledge primarily comes from model organisms like mice, with potential species-specific differences in humans.

Purpose of the Study:

  • To generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development.
  • To investigate the interrelationships between DNA methylation, chromatin states, and gene expression in early human embryos.

Main Methods:

  • Application of single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq).
  • Genome-wide mapping of DNA methylation and chromatin accessibility.
  • Single-cell resolution analysis of human preimplantation embryos.

Main Results:

  • Unlike mice, human paternal genome chromatin is more open than maternal chromatin from the mid-zygote to 4-cell stage.
  • Sets of genes with high DNA methylation variation differ from those with high chromatin accessibility variation.
  • Inhibition of transcription led to the closure of 35% of open promoter regions, suggesting a transcription-chromatin feedback mechanism.

Conclusions:

  • This study provides the first comprehensive single-cell epigenetic landscape of human preimplantation development.
  • Identified species-specific epigenetic reprogramming patterns in humans compared to mice.
  • Revealed a feedback mechanism linking transcription and chromatin accessibility maintenance in early human development.