@article {Xia2023-dj,
	title = {Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation},
	journal = {Nat. Commun.},
	volume = {14},
	number = {1},
	year = {2023},
	pages = {6295},
	publisher = {Springer Science and Business Media LLC},
	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.},
	author = {Xia, Lei and Komissarova, Anastasia and Jacover, Arielle and Shovman, Yehuda and Arcila-Barrera, Sebastian and Tornovsky-Babeay, Sharona and Jaya Prakashan, Milsee Mol and Nasereddin, Abdelmajeed and Plaschkes, Inbar and Nevo, Yuval and Shiff, Idit and Yosefov-Levi, Oshri and Izhiman, Tamara and Medvedev, Eleonora and Eilon, Elad and Wilensky, Asaf and Yona, Simon and Parnas, Oren}
}
