Dynamic regulatory network controlling T(H)17 cell differentiation

Article

关键词: GENOME-WIDE ANALYSIS;    TRANSCRIPTION-FACTOR;    GENE-EXPRESSION;    T-CELLS;    TARGET GENES;    PLATFORM;    GAMMA;    INDUCTION;    DISCOVERY;    DATABASE;   

DOI  :  10.1038/nature11981

来源: SCIE

【 摘 要 】

Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse T(H)17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The T(H)17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between T(H)17 and other CD41 T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling T(H)17 cell differentiation.

【 授权许可】

Free