A single-cell atlas of chromatin accessibility in mouse organogenesis

Nat Cell Biol. 2024 Jul;26(7):1200-1211. doi: 10.1038/s41556-024-01435-6. Epub 2024 Jul 8.

Abstract

Organogenesis is a highly complex and precisely regulated process. Here we profiled the chromatin accessibility in >350,000 cells derived from 13 mouse embryos at four developmental stages from embryonic day (E) 10.5 to E13.5 by SPATAC-seq in a single experiment. The resulting atlas revealed the status of 830,873 candidate cis-regulatory elements in 43 major cell types. By integrating the chromatin accessibility atlas with the previous transcriptomic dataset, we characterized cis-regulatory sequences and transcription factors associated with cell fate commitment, such as Nr5a2 in the development of gastrointestinal tract, which was preliminarily supported by the in vivo experiment in zebrafish. Finally, we integrated this atlas with the previous single-cell chromatin accessibility dataset from 13 adult mouse tissues to delineate the developmental stage-specific gene regulatory programmes within and across different cell types and identify potential molecular switches throughout lineage development. This comprehensive dataset provides a foundation for exploring transcriptional regulation in organogenesis.

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Mice
  • Mice, Inbred C57BL
  • Organogenesis* / genetics
  • Single-Cell Analysis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome / genetics
  • Zebrafish* / embryology
  • Zebrafish* / genetics
  • Zebrafish* / metabolism

Substances

  • Chromatin
  • Transcription Factors