| First Author | Yosef N | Year | 2013 |
| Journal | Nature | Volume | 496 |
| Issue | 7446 | Pages | 461-8 |
| PubMed ID | 23467089 | Mgi Jnum | J:241283 |
| Mgi Id | MGI:5898455 | Doi | 10.1038/nature11981 |
| Citation | Yosef N, et al. (2013) Dynamic regulatory network controlling TH17 cell differentiation. Nature 496(7446):461-8 |
| abstractText | 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 TH17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH17 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 TH17 and other CD4(+) 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 TH17 cell differentiation. |
