Simultaneous profiling of gene expression and chromatin accessibility in single cells.

Profiling multiple omic layers in a single cell enables the discovery and analysis of biological phenomena that are not apparent from analysis of mono-omic data. While methods for multi-omic profiling have been reported, their adoption has been limited due to high cost and complex workflows. Here, we present a simple method for joint profiling of gene expression and chromatin accessibility in tens to hundreds of single cells. We assess the quality of resulting single cell ATAC- and RNA-seq data across three cell types, examine the link between accessibility and expression at the CD3G and FTH1 loci in human primary T cells and monocytes, and compare the accuracy of clustering solutions for mono-omic and combined data. The new method allows biological laboratories to perform simultaneous profiling of gene expression and chromatin accessibility using standard reagents and instrumentation. This technique, in conjunction with other advances in multi-omic profiling, will enable highly-resolved cell state classification and more specific mechanistic hypothesis generation than is possible with mono-omic analysis.