Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2

Science. 2025 Mar 28;387(6741):eadp4319. doi: 10.1126/science.adp4319. Epub 2025 Mar 28.

Abstract

In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. Here, we developed scNanoATAC-seq2, a single-cell assay for transposase-accessible chromatin using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and two-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in noncanonical imprinting, imprinted X chromosome inactivation, and low-mappability genomic regions, such as repetitive elements and paralogs. Our data provide insights into chromatin dynamics during mammalian preimplantation development and lineage differentiation.

MeSH terms

  • Animals
  • Blastocyst* / metabolism
  • Cell Lineage
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Embryonic Development* / genetics
  • Endoderm / metabolism
  • Epigenesis, Genetic
  • Female
  • Genomic Imprinting
  • Germ Layers / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Single-Cell Analysis* / methods
  • Transposases / metabolism
  • X Chromosome Inactivation
  • Zygote / metabolism

Substances

  • Chromatin
  • Transposases