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A scalable platform for the development of cell-type-specific viral drivers.

ABSTRACT: 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.

SUBMITTER: Hrvatin S

PROVIDER: S-EPMC6776442 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A scalable platform for the development of cell-type-specific viral drivers.

Hrvatin Sinisa S Tzeng Christopher P CP Nagy M Aurel MA Stroud Hume H Koutsioumpa Charalampia C Wilcox Oren F OF Assad Elena G EG Green Jonathan J Harvey Christopher D CD Griffith Eric C EC Greenberg Michael E ME

eLife 20190923

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 sin ...[more]

PMID: 31545165

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Dataset Information

A scalable platform for the development of cell-type-specific viral drivers.

Publications

A scalable platform for the development of cell-type-specific viral drivers.

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