Rxivist logo

Genome-wide CRISPR screens in T helper cells reveal pervasive cross-talk between activation and differentiation

By Johan Henriksson, Xi Chen, T Gomes, Ubaid Ullah, Kerstin B Meyer, Ricardo Miragaia, Graham Duddy, Jhuma Pramanik, Kosuke Yusa, Riitta Lahesmaa, Sarah A Teichmann

Posted 04 Oct 2017
bioRxiv DOI: 10.1101/196022

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 (including 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 is only a small number of genes regulating differentiation without any role in activation. Our study provides an atlas for the T helper cell regulatory network, pinpointing key players of Th2 differentiation and demonstrating remarkable plasticity between the diverse T helper cell fates. We provide an online resource for interactive data querying at: http://data.teichlab.org.

Download data

  • Downloaded 3,269 times
  • Download rankings, all-time:
    • Site-wide: 1,665 out of 93,322
    • In immunology: 53 out of 2,773
  • Year to date:
    • Site-wide: 22,524 out of 93,322
  • Since beginning of last month:
    • Site-wide: 21,308 out of 93,322

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)