Gene regulatory landscape dissected by single-cell four-omics sequencing

The diversity of cell types is not only determined by the transcriptome, but also encoded by multiple layers of epigenomic programs including nucleosome occupancy, chromatin states and genome architecture. To comprehensively understand how these regulatory modalities converge to shape cellular identity, we developed CHARM, a single-cell four-omics sequencing technique that enables parallel profiling of genome conformation, histone modifications, chromatin accessibility, and gene expression in the same cell.We applied CHARM to mouse embryonic stem cells and cortical tissues. The same cell contains two libraries, one of which mainly contains Hi-C data, while the other is enriched with RNA/histone modification/accessibility data.