Systematic CRISPR screens in primary human T cells uncovered the upstream regulators of crucial immune genes — IL2RA, IL2 and CTLA4. Then, using RNA-seq and ATAC-seq in knockout T cells, we mapped the downstream target genes and non-coding cis-regulatory elements of key regulators, thereby revealing a regulatory network enriched for immune disease-associated genes.
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References
Liu, X., Li, Y. I. & Pritchard, J. K. Trans effects on gene expression can drive omnigenic inheritance. Cell 177, 1022–1034.e6 (2019). This paper hypothesizes that many disease-associated genetic variants act through trans-regulatory networks.
Schumann, K. et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc. Natl Acad. Sci. USA 112, 10437–10442 (2015). This paper introduces a method for the efficient generation of gene knockouts in primary human T cells using Cas9 ribonucleoproteins.
Shifrut, E. et al. Genome-wide CRISPR screens in primary human t cells reveal key regulators of immune function. Cell 175, 1958–1971.e15 (2018). This paper introduces a method for performing pooled CRISPR screens efficiently in primary human T cells.
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This is a summary of: Freimer, J. W. et al. Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks. Nat. Genet. https://doi.org/10.1038/s41588-022-01106-y (2022).
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Mapping the regulators of key immune genes and disease networks. Nat Genet 54, 1070–1071 (2022). https://doi.org/10.1038/s41588-022-01107-x
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DOI: https://doi.org/10.1038/s41588-022-01107-x