A1 Refereed original research article in a scientific journal
Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation
Authors: Henriksson J, Chen X, Gomes T, Ullah U, Meyer KB, Miragaia R, Duddy G, Pramanik J, Yusa K, Lahesmaa R, Teichmann SA
Publisher: CELL PRESS
Publication year: 2019
Journal: Cell
Journal name in source: CELL
Journal acronym: CELL
Volume: 176
Issue: 4
First page : 882
Number of pages: 33
ISSN: 0092-8674
eISSN: 1097-4172
DOI: https://doi.org/10.1016/j.cell.2018.11.044
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/39704856
T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, autoimmunity, and tumor immunology. Using a newly developed, genome-wide retroviral CRISPR knockout (KO) library, combined with RNA-seq, ATAC-seq, and ChIP-seq, we have dissected the regulatory circuitry governing activation 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 factors, such as Pparg and BhThe40, as part of the core regulatory network governing Th2 helper cell fates.
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