TY - JOUR TI - A scalable platform for the development of cell-type-specific viral drivers AU - Hrvatin, Sinisa AU - Tzeng, Christopher P AU - Nagy, M Aurel AU - Stroud, Hume AU - Koutsioumpa, Charalampia AU - Wilcox, Oren F AU - Assad, Elena G AU - Green, Jonathan AU - Harvey, Christopher D AU - Griffith, Eric C AU - Greenberg, Michael E A2 - West, Anne E A2 - Dulac, Catherine VL - 8 PY - 2019 DA - 2019/09/23 SP - e48089 C1 - eLife 2019;8:e48089 DO - 10.7554/eLife.48089 UR - https://doi.org/10.7554/eLife.48089 AB - Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research. KW - enhancers KW - AAV KW - cell-type-specific KW - somatostatin KW - PESCA JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -