Evidence map›Paper›PMID 26189680›Full record

ArticleCell2015

A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks.

Oren Parnas, Marko Jovanovic, Thomas M Eisenhaure, Rebecca H Herbst, Atray Dixit, Chun Jimmie Ye, Dariusz Przybylski, Randall J Platt, Itay Tirosh, Neville E Sanjana and 8 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers.

0numbers the graph read from it
0cells of the map it votes in
291citing papers in PubMed
25.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

291 citing papers in PubMed, 451 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Cas9eLife · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Functional Genomics: Principles and Methods.Advances in experimental medicine and biology · 2026
    Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

231 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Oren ParnasBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Marko JovanovicBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Thomas M EisenhaureBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Rebecca H HerbstBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.
Atray DixitBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
Chun Jimmie YeInstitute for Human Genetics, Department of Epidemiology and Biostatistics, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Dariusz PrzybylskiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Randall J PlattBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Itay TiroshBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Neville E SanjanaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ophir ShalemBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rahul SatijaNew York Genome Center, New York, NY 10013, USA; New York University, Center for Genomics and Systems Biology, New York, NY 10012, USA.
Raktima RaychowdhuryBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Philipp MertinsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Feng ZhangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston MA 02114. Electronic address: nhacohen@broadinstitute.org.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02140, USA. Electronic address: aregev@broadinstitute.org.
Broad Institute · USNew York Genome Center · USUniversity of California, San Francisco · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ANDREW D LUSTER · 1991 to 2026
$35.3M
Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease MutationsR01DK097768 · NIDDK · BROAD INSTITUTE, INC. · PI COWAN, CHAD ALBERT, ZHANG, FENG · 2012 to 2016
$11.0M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
Genome engineering tools for functional screening of non-coding elementsK99HG008171 · NHGRI · BROAD INSTITUTE, INC. · PI SANJANA, NEVILLE · 2015 to 2016
$125k
Howard Hughes Medical InstituteNCCDPHP CDC HHS 5DP1-MH100706NHGRI NIH HHS K99 HG008171NHGRI NIH HHS K99-HG008171NHGRI NIH HHS P50 HG006193NIDDK NIH HHS 5R01-DK097768NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097768NIMH NIH HHS DP1 MH100706NIMH NIH HHS R01 MH110049
6 · The paper itself

Abstract

Finding the components of cellular circuits and determining their functions systematically remains a major challenge in mammalian cells. Here, we introduced genome-wide pooled CRISPR-Cas9 libraries into dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (Tnf) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the Tlr4 pathway. We found many of the known regulators of Tlr4 signaling, as well as dozens of previously unknown candidates that we validated. By measuring protein markers and mRNA profiles in DCs that are deficient in known or candidate genes, we classified the genes into three functional modules with distinct effects on the canonical responses to LPS and highlighted functions for the PAF complex and oligosaccharyltransferase (OST) complex. Our findings uncover new facets of innate immune circuits in primary cells and provide a genetic approach for dissection of mammalian cell circuits.

Indexed as

CRISPR-Cas SystemsGenetic TechniquesImmunity, InnateAnimalsBone Marrow CellsCell DifferentiationCell SurvivalDendritic CellsGene Knockout TechniquesGene Regulatory NetworksHexosyltransferasesMembrane ProteinsMiceMice, TransgenicToll-Like Receptor 4Tumor Necrosis Factor-alphadolichyl-diphosphooligosaccharide - protein glycotransferaseHexosyltransferasesMembrane ProteinsTlr4 protein, mouseToll-Like Receptor 4Tumor Necrosis Factor-alpha

Identifiers

PMID26189680
PMCPMC4522370
OpenAlexW2106296224

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.