PT  - JOURNAL ARTICLE
AU  - Sinisa Hrvatin
AU  - Christopher P. Tzeng
AU  - M. Aurel Nagy
AU  - Hume Stroud
AU  - Charalampia Koutsioumpa
AU  - Oren F. Wilcox
AU  - Eric C. Griffith
AU  - Michael E. Greenberg
TI  - PESCA: A scalable platform for the development of cell-type-specific viral drivers
AID  - 10.1101/570895
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 570895
4099  - http://biorxiv.org/content/early/2019/03/08/570895.short
4100  - http://biorxiv.org/content/early/2019/03/08/570895.full
AB  - Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression, thus giving rise to the hundreds of different cell types that make up a complex organism. 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 such enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method coupling ATAC and single-cell RNA sequencing protocols, to identify cell-type-specific enhancers that should enable genetic access and perturbation of gene function in virtually any mammalian cell type. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a rare subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this readily generalizable platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.