A scalable platform for the development of cell-type-specific viral drivers
Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.48089
Institution: Harvard University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: A General Approach for the Development of New Cell-Type-Specific Viral Vectors, New approaches to understand neuronal microcircuit dynamics for working memory, Medical Scientist Training Program, Studying perceptual decision-making across cortex by combining population imaging, connectomics, and computational modeling, Parietal Cortex Networks for Sensorimotor Processing During Navigation, G5632063321, G9000353262, Training in the Molecular Biology of Neurodegeneration and Alzheimer's Disease
OpenAlex ID: W2975034635