RT Journal Article
SR Electronic
T1 An unbiased reconstruction of the T helper cell type 2 differentiation network
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 196022
DO 10.1101/196022
A1 Johan Henriksson
A1 Xi Chen
A1 Tomás Gomes
A1 Kerstin Meyer
A1 Ricardo Miragaia
A1 Ubaid Ullah
A1 Jhuma Pramanik
A1 Riita Lahesmaa
A1 Kosuke Yusa
A1 Sarah A Teichmann
YR 2017
UL http://biorxiv.org/content/early/2017/10/04/196022.abstract
AB T helper type 2 (Th2) cells are important regulators of our adaptive immune response, particularly the response against parasites, and have relevance for auto-immunity as well as tumour progression. This classic T helper type has been studied intensively, but not systematically. Using newly developed, genome-wide retroviral CRISPR knock-out (KO) technology, combined with RNA-seq, ATAC-seq and ChIP-seq, we have dissected the regulatory circuitry governing differentiation in these cells. During Th2 activation/differentiation approximately 4000 genes are perturbed, with at least 200 genes specifically associated with the Th2 program in mouse and human. We confirm previously known Th2 driver genes and have discovered several novel genes, including transcription factors, metabolic genes and potential receptors/cytokines, critical for Th2 function. Our study provides an atlas for, but not limited to, the Th2 regulatory network, pinpointing the key players of Th2 differentiation.