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CRISPR activation and interference screens decode stimulation responses in primary human T cells [Bulk RNA-seq]

ABSTRACT: CRISPR activation and interference screens decode stimulation responses in primary human T cells [Bulk RNA-seq]

PROVIDER: PRJNA729100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14517719_1.fastq.gz	Fastqsanger.gz
	SRR14517719_2.fastq.gz	Fastqsanger.gz
	SRR14517720_1.fastq.gz	Fastqsanger.gz
	SRR14517720_2.fastq.gz	Fastqsanger.gz
	SRR14517721_1.fastq.gz	Fastqsanger.gz

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

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CRISPR activation and interference screens decode stimulation responses in primary human T cells [Bulk RNA-seq]

Project description: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 and interferon gamma production. Arrayed CRISPRa confirmed key hits and enabled multiplexed secretome characterization, revealing reshaped cytokine responses. Coupling CRISPRa screening with single-cell RNA-seq enabled deep molecular characterization of screen hits, revealing how perturbations tuned T cell activation and promoted cell states characterized by distinct cytokine expression profiles. Together, these screens reveal genes that reprogram critical immune cell functions, which could inform the design of immunotherapies.

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CRISPR activation and interference screens decode stimulation responses in primary human T cells [CRISPRa Perturb-seq]

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Project description: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.

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

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