Simultaneous profiling of chromatin architecture and transcription in single cells

Three-dimensional (3D) chromatin structure plays a crucial role in development and diseases, which are associated with transcriptional changes. However, given the heterogeneity in single-cell chromatin architecture and transcription, the regulatory relationship between 3D chromatin structure and gene expression is difficult to explain based on the cell populations. Here we developed a single-cell multimodal omics method for simultaneously detecting chromatin architecture and mRNA expression by sequencing (scCARE-seq). Applying scCARE-seq to examine chromatin architecture and transcription from naïve to primed single mouse embryonic stem cells (mESCs), we observed correlated changes between 3D chromatin structure and expression in the cell fate transition. In addition, we defined cell cycle phase of each cell through chromatin architecture extracted by CARE-seq, and found that periodic changes in chromatin architecture were in parallel with transcription during the cell cycle. These findings indicate that scCARE-seq allows comprehensive analysis of chromatin architecture and transcription in the same single cell. Overall design: chromatin architecture and gene expression profiling by high throughput sequencing