CRISPR activation and interference screens decode stimulation responses in primary human T cells.
Science
; 375(6580): eabj4008, 2022 02 04.
Article
en En
| MEDLINE
| ID: mdl-35113687
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
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Linfocitos T
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Interferón gamma
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Interleucina-2
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Redes Reguladoras de Genes
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Sistemas CRISPR-Cas
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Proteína 9 Asociada a CRISPR
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos