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Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation.
- Source :
- Nature Communications; 10/9/2023, Vol. 14 Issue 1, p1-19, 19p
- Publication Year :
- 2023
-
Abstract
- Genetic engineering of immune cells has opened new avenues for improving their functionality but it remains a challenge to pinpoint which genes or combination of genes are the most beneficial to target. Here, we conduct High Multiplicity of Perturbations and Cellular Indexing of Transcriptomes and Epitopes (HMPCITE-seq) to find combinations of genes whose joint targeting improves antigen-presenting cell activity and enhances their ability to activate T cells. Specifically, we perform two genome-wide CRISPR screens in bone marrow dendritic cells and identify negative regulators of CD86, that participate in the co-stimulation programs, including Chd4, Stat5b, Egr2, Med12, and positive regulators of PD-L1, that participate in the co-inhibitory programs, including Sptlc2, Nckap1l, and Pi4kb. To identify the genetic interactions between top-ranked genes and find superior combinations to target, we perform high-order Perturb-Seq experiments and we show that targeting both Cebpb and Med12 results in a better phenotype compared to the single perturbations or other combinations of perturbations. Determining targets for genetic engineering of immune cells remains a challenge. Here, we apply genome-wide CRISPR screens with a high-order Perturb-seq (named HMPCITE-seq) to identify gene combinations whose joint targeting improves innate immune cell function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 172866708
- Full Text :
- https://doi.org/10.1038/s41467-023-41792-8