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

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

PROVIDER: PRJNA787633 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17189067_1.fastq.gz	Fastqsanger.gz
	SRR17189067_2.fastq.gz	Fastqsanger.gz
	SRR17189068_1.fastq.gz	Fastqsanger.gz
	SRR17189068_2.fastq.gz	Fastqsanger.gz
	SRR17189069_1.fastq.gz	Fastqsanger.gz

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

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

| PRJNA787633 | ENA

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

2022-02-04 | GSE190604 | GEO

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

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

2022-02-04 | GSE190846 | GEO

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

2021-05-13 | GSE174284 | GEO

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

Project description: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 [CRISPR]

Project description:CRISPR activation and interference screens decode stimulation responses in primary human T cells [CRISPR]

| PRJNA728974 | ENA

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

Project description:CRISPR activation and interference screens decode stimulation responses in primary human T cells [Supplemental CRISPR]

| PRJNA788572 | ENA

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

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

| PRJNA729100 | ENA

Compressed Perturb-seq: highly efficient screens for regulatory circuits using random composite perturbations

Project description:Pooled CRISPR screens with single-cell RNA-seq readout (Perturb-seq) have emerged as a key technique in functional genomics, but are limited in scale by cost and combinatorial complexity. Here, we reimagine Perturb-seq’s design through the lens of algorithms applied to random, low-dimensional observations. We present compressed Perturb-seq, in which we measure multiple perturbations per cell or multiple cells per droplet, and decompress these measurements by leveraging the sparse structure of regulatory circuits. Applying compressed Perturb-seq to 598 genes in the immune response to bacterial lipopolysaccharide, we achieve the same accuracy as conventional Perturb-seq at 4 to 20-fold reduced cost, with greater power to learn genetic interactions. We identify known and novel regulators of immune responses and uncover evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing GWAS or trans-eQTL studies. Our framework enables new scales of interrogation for a foundational method in functional genomics.

2023-01-01 | GSE221321 | GEO

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