Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation

J Henriksson, X Chen, T Gomes, U Ullah, Meyer K B, R Miragaia, G Duddy, J Pramanik, K Yusa, Riitta Lahesmaa, Teichmann S A

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

119 Sitaatiot (Scopus)

Abstrakti

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.
AlkuperäiskieliEi tiedossa
Sivut882–896
Sivumäärä33
JulkaisuCell
Vuosikerta176
Numero4
DOI - pysyväislinkit
TilaJulkaistu - 2019
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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