ArticleCell2016
A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response.
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Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 740 papers.
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740citing papers in PubMed
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Who cites it
740 citing papers in PubMed.
- Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Testing the Transferability of Perturbational Similarity Maps Across Species, Cell Systems, and Assay Modalities.Neuroinformatics · 2026Article
- Host chromatin architecture in HPV-driven cervical cancer: molecular mechanisms and therapeutic resistance.Medical oncology (Northwood, London, England) · 2026Review
- scLDM: a conditional diffusion framework for single-cell perturbation prediction.Bioinformatics (Oxford, England) · 2026Article
- Review
- A high-throughput co-culture CRISPR array for rapid fitness hypothesis testing and growth engineering in CHO cells.iScience · 2026Article
- A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.Cancer cell · 2026Article
- A systematic comparison of single-cell perturbation response prediction models.Science advances · 2026Article
- CRISPRing through time: How cutting-edge technology is revolutionizing life sciences and medicine.Molecular therapy. Nucleic acids · 2026Review
- A transcription factor regulatory atlas for activity inference and perturbation prediction.Nucleic acids research · 2026Article
- Benchmarking methods for inferring single-cell transcription factor activity using large-scale perturbation sequencing data.Briefings in bioinformatics · 2026Article
- Characterizing and mitigating cross-library PCR chimeras in Perturb-seq using Perturb-Audit.Blood science (Baltimore, Md.) · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Induced pluripotent stem cells from discovery to translation.Nature medicine · 2026Review
- Article
- Data-centric feedback loops for next-generation immunotherapy development.Nature biomedical engineering · 2026Review
- scGPA: an LLM-assisted workflow for directional virtual gene perturbation analysis from single-cell transcriptomes.BMC genomics · 2026Article
- A Functional Atlas of Transcription Factor-Driven Astrocyte States In Vivo.Neuroscience bulletin · 2026Article
- Sensitivity analysis of cell fate trajectories from single-cell transcriptomics.Bioinformatics (Oxford, England) · 2026Article
- Decoding Cardiac Development and Maturation at Single-Cell and Spatial Transcriptomic Resolution.Circulation research · 2026Review
680 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors.
Britt AdamsonDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Thomas M NormanDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Marco JostDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Min Y ChoDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
James K NuñezDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Yuwen ChenDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Jacqueline E VillaltaDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Luke A GilbertDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Max A HorlbeckDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Marco Y HeinDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Ryan A PakDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Innovative Genomics Initiative, University of California, Berkeley, Berkeley, CA 94720, USA.
Andrew N GrayDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Carol A GrossDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Integrative Program in Quantitative Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Atray DixitHarvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02142, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Oren ParnasBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
Jonathan S WeissmanDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jonathan.weissman@ucsf.edu.
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6MCenter for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6MCenter for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9MPROJECT 3P50GM102706 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2012 to 2016
$9.5MCellular homeostasis pathways in bacteriaR35GM118061 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GROSS, CAROL ANNE · 2016 to 2025
$9.0MBay Area Cancer Target Discovery and Development NetworkU01CA168370 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCCORMICK, FRANK PATRICK, MCMANUS, MICHAEL T · 2012 to 2016
$3.9MIntegrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2MHarnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9MGene Function and Pathway Analysis Using Systems Level Approaches in ProkaryotesR01GM102790 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GROSS, CAROL ANNE · 2012 to 2015
$1.8MHuman Gene Knockdowns that May Extend LifespanR01AG041826 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEISSMAN, JONATHAN S. · 2012 to 2016
$1.6MA functional genomics approach to determine the mechanism of cellular response to new anti-cancer R00CA204602 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2017 to 2019
$747kSystematic Genome-Wide Characterization of Iron HomeostasisF32GM116331 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOST, MARCO · 2015 to 2017
$162kHoward Hughes Medical InstituteNCI NIH HHS K99 CA204602NCI NIH HHS R00 CA204602NCI NIH HHS U01 CA168370NHGRI NIH HHS P50 HG006193NHGRI NIH HHS RM1 HG006193NIA NIH HHS R01 AG041826NIBIB NIH HHS T32 EB009383NIDA NIH HHS R01 DA036858NIGMS NIH HHS F32 GM116331NIGMS NIH HHS P50 GM102706NIGMS NIH HHS R01 GM102790NIGMS NIH HHS R35 GM118061NIGMS NIH HHS T32 GM007618
Abstract
Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ∼100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses.
Indexed as
AnimalsClustered Regularly Interspaced Short Palindromic RepeatsEndoribonucleasesFeedbackHumansModels, MolecularProtein Serine-Threonine KinasesRNA, Guide, CRISPR-Cas SystemsSequence Analysis, RNASingle-Cell AnalysisTranscription, GeneticUnfolded Protein ResponseEndoribonucleasesERN1 protein, humanProtein Serine-Threonine KinasesRNA, Guide, CRISPR-Cas Systemscell-to-cell heterogeneityCRIPSRiCRISPRgenome-scale screeningsingle-cell genomicsSingle-cell RNA-sequnfolded protein response
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