@article{3397, keywords = {Animals, Mice, Gene Expression Profiling, Sequence Analysis, RNA, Humans, Transcription Factors, Feedback, Cell Cycle, Mice, Transgenic, Single-Cell Analysis, Gene Knockdown Techniques, Clustered Regularly Interspaced Short Palindromic Repeats, K562 Cells}, author = {Atray Dixit and Oren Parnas and Biyu Li and Jenny Chen and Charles Fulco and Livnat Jerby-Arnon and Nemanja Marjanovic and Danielle Dionne and Tyler Burks and Raktima Raychowdhury and Britt Adamson and Thomas Norman and Eric Lander and Jonathan Weissman and Nir Friedman and Av Regev iv}, title = {Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens.}, abstract = {

Genetic screens help infer gene function in mammalian cells, but it has remained difficult to assay complex phenotypes-such as transcriptional profiles-at scale. Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. We demonstrate Perturb-seq by analyzing 200,000 cells in immune cells and cell lines, focusing on transcription factors regulating the response of dendritic cells to lipopolysaccharide (LPS). Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and~their genetic interactions. We posit new functions for regulators of differentiation, the anti-viral response, and mitochondrial function during immune activation. By decomposing many high content measurements into the effects of perturbations, their interactions, and diverse cell metadata, Perturb-seq dramatically increases the scope of pooled genomic assays.

}, year = {2016}, journal = {Cell}, volume = {167}, pages = {1853-1866.e17}, month = {2016 Dec 15}, issn = {1097-4172}, doi = {10.1016/j.cell.2016.11.038}, language = {eng}, }