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

Remarkable 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 3D genome structures, despite being heavily determined by the cell cycle and developmental stages, gradually diverged in a cell-type-specific manner as development progressed. We further developed a computational pipeline to identify and link differential chromatin interactions to their relevant genes based on covariation of interaction strength and transcription activity. By comparing the pseudo temporal dynamics of chromatin interactions with gene expression, we found a widespread chromatin rewiring that occurred prior to transcription activation. Our results demonstrate that the establishment of specific chromatin interactions are tightly related to transcriptional control and cell functions during lineage specification. Using Hi-C and RNA-seq to analyze single cells from mouse embryos and mouse brains.