A scalable technology for measuring cell-typespecific activity of cis-regulatory sequences

Most perturbations to the Gnb3 promoter affected all four cell types uniformly, but certain perturbations to specific binding sites for CRX (a homeodomain protein required for Gnb3 expression) resulted in cell-type-specific effects. [...]perturbations to some CRX binding sites affected gene expression in all cell types, whereas perturbations in others had effects only in specific cell types (Fig. 1c,d). Future directions Most disease-causing variation identified in genome wide association studies (GWASs) maps to non-coding portions of the human genome, and these variants are thought to influence the activities of cell-type-specific CRSs2. Typical scRNA-seq experiments assess 10,000-40,000 cells, and our experiments show that each CRS must be measured in ~70 individual cells to obtain reproducible results. [...]if the cell type of interest is rare in a tissue, it will be difficult to obtain robust measurements with scMPRA without enriching for that cell type.