Evidence map›Paper›PMID 35113687›Full record

ArticleScience (New York, N.Y.)2022

CRISPR activation and interference screens decode stimulation responses in primary human T cells.

Ralf Schmidt, Zachary Steinhart, Madeline Layeghi, Jacob W Freimer, Raymund Bueno, Vinh Q Nguyen, Franziska Blaeschke, Chun Jimmie Ye, Alexander Marson

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
200citing papers in PubMed, 2 pooled it
23.7field-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

200 citing papers in PubMed, 2 syntheses or guidelines pooled it, 296 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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  6. Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  7. Article
  8. Article
  9. Genome-scale perturbation signatures from primary human CD4bioRxiv : the preprint server for biology · 2026
    Article
  10. Review
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  12. Article
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  14. Article
  15. Article
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140 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Ralf Schmidt *Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0002-6697-0363
Zachary Steinhart *Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0002-7344-5700
Madeline LayeghiGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0003-3757-4107
Jacob W FreimerGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0001-9239-2272
Raymund BuenoDepartment of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8534-9399
Vinh Q NguyenDepartment of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Franziska BlaeschkeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0001-5770-4744
Chun Jimmie YeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0001-6560-3783
Alexander MarsonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.ORCID 0000-0002-2734-5776
Gladstone Institutes · USUniversity of California, San Francisco · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
Integration of genetic association mapping and functional data to elucidate genetic mechanisms of diseaseR01HG008140 · NHGRI · STANFORD UNIVERSITY · PI JONATHAN K PRITCHARD · 2016 to 2026
$7.3M
Functional Interrogation of Non-Coding Type 1 Diabetes Risk Variants in Human Immune Cells and Beta CellsDP3DK111914 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSON, ALEXANDER · 2016 to 2016
$3.7M
BD FACSAria Fusion Cell SorterS10OD021822 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, MICHAEL R. · 2016 to 2016
$573k
BD FACSAria II Flow CytometerS10RR028962 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI CAVROIS, MARIELLE · 2011 to 2011
$544k
NCRR NIH HHS S10 RR028962NHGRI NIH HHS R01 HG008140NIDDK NIH HHS DP3 DK111914NIDDK NIH HHS P30 DK063720NIH HHS S10 OD021822
6 · The paper itself

Abstract

Regulation of cytokine production in stimulated T cells can be disrupted in autoimmunity, immunodeficiencies, and cancer. Systematic discovery of stimulation-dependent cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now report genome-wide CRISPR activation (CRISPRa) and interference (CRISPRi) screens in primary human T cells to identify gene networks controlling interleukin-2 (IL-2) and interferon-γ (IFN-γ) production. Arrayed CRISPRa confirmed key hits and enabled multiplexed secretome characterization, revealing reshaped cytokine responses. Coupling CRISPRa screening with single-cell RNA sequencing enabled deep molecular characterization of screen hits, revealing how perturbations tuned T cell activation and promoted cell states characterized by distinct cytokine expression profiles. These screens reveal genes that reprogram critical immune cell functions, which could inform the design of immunotherapies.

Indexed as

CRISPR-Cas SystemsGene Regulatory NetworksLymphocyte ActivationCell LineCells, CulturedCRISPR-Associated Protein 9Gene Expression RegulationGenome, HumanHumansInterferon-gammaInterleukin-2NF-kappa BRNA-SeqSignal TransductionSingle-Cell AnalysisT-LymphocytesCRISPR-Associated Protein 9IL2 protein, humanInterferon-gammaInterleukin-2NF-kappa B

Identifiers

PMID35113687
PMCPMC9307090
OpenAlexW4210396037

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.