Human Gene Set: GSE43955_TH0_VS_TGFB_IL6_IL23_TH17_ACT_CD4_TCELL_52H_DN


Standard name GSE43955_TH0_VS_TGFB_IL6_IL23_TH17_ACT_CD4_TCELL_52H_DN
Systematic name M9653
Brief description Genes down-regulated in CD4 [GeneID=920] T helper cells (52h): Th0 versus Th17 treated with TGFB1, IL6 [GeneID=7040;3569] and IL-23.
Full description or abstract Despite their enormous importance, the molecular circuits that control the differentiation of Th17 cells remain largely unknown. Recent studies have reconstructed regulatory networks in mammalian cells, but have focused on short-term responses and relied on perturbation approaches that cannot be applied to primary T cells. Here, we develop a systematic strategy ? combining transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based tools for performing gene perturbations in primary T cells ? to derive and experimentally validate a temporal model of the dynamic regulatory network that controls Th17 differentiation. The network is arranged into two self-reinforcing and mutually antagonistic modules that either suppress or promote Th17 differentiation. The two modules contain 12 novel regulators with no previous implication in Th17 differentiation, which may be essential to maintain the appropriate balance of Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors that are embedded within a comprehensive temporal network and identifies novel drug targets and organizational principles for the differentiation of Th17 cells.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 23467089   Authors: Yosef N,Shalek AK,Gaublomme JT,Jin H,Lee Y,Awasthi A,Wu C,Karwacz K,Xiao S,Jorgolli M,Gennert D,Satija R,Shakya A,Lu DY,Trombetta JJ,Pillai MR,Ratcliffe PJ,Coleman ML,Bix M,Tantin D,Park H,Kuchroo VK,Regev A
Exact source GSE43955_2424_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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