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

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.