Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq

Science. 2023 Jun 9;380(6649):1070-1076. doi: 10.1126/science.adg3797. Epub 2023 Jun 8.

Abstract

Much progress has been made recently in single-cell chromosome conformation capture technologies. However, a method that allows simultaneous profiling of chromatin architecture and gene expression has not been reported. Here, we developed an assay named "Hi-C and RNA-seq employed simultaneously" (HiRES) and performed it on thousands of single cells from developing mouse embryos. Single-cell three-dimensional genome structures, despite being heavily determined by the cell cycle and developmental stages, gradually diverged in a cell type-specific manner as development progressed. By comparing the pseudotemporal dynamics of chromatin interactions with gene expression, we found a widespread chromatin rewiring that occurred before transcription activation. Our results demonstrate that the establishment of specific chromatin interactions is tightly related to transcriptional control and cell functions during lineage specification.

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Chromatin* / chemistry
  • Chromatin* / genetics
  • Embryo, Mammalian
  • Embryonic Development* / genetics
  • Gene Expression Regulation, Developmental
  • Genome*
  • Mice
  • RNA-Seq* / methods
  • Single-Cell Analysis* / methods

Substances

  • Chromatin