Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation
Creators
- 1. Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom
Description
T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, auto-immunity and tumour immunology. Using a newly developed, genome-wide retroviral CRISPR knock-out (KO) library, combined with RNA-seq, ATAC-seq and ChIP-seq, we have dissected the regulatory circuitry governing activation/proliferation and differentiation of these cells. Our experiments distinguish cell activation versus differentiation in a quantitative framework. We demonstrate that these two processes are tightly coupled and are jointly controlled by many transcription factors, metabolic genes and cytokine/receptor pairs. There are only a small number of genes regulating differentiation without any role in activation. By combining biochemical and genetic data, we provide an atlas for Th2 differentiation, validating known regulators and identifying novel players, such as Pparg and Bhlhe40, that are part of the core regulatory network governing Th2 helper cell fates.
Files
Files
(4.6 MB)
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