Dynamic regulatory network controlling Th17 cell differentiation

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Dynamic regulatory network controlling Th17 cell differentiation

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Title: Dynamic regulatory network controlling Th17 cell differentiation
Author: Yosef, Nir; Shalek, Alex K.; Gaublomme, Jellert T.; Jin, Hulin; Lee, Youjin; Awasthi, Amit; Wu, Chuan; Karwacz, Katarzyna; Xiao, Sheng; Jorgolli, Marsela; Gennert, David; Satija, Rahul; Shakya, Arvind; Lu, Diana Y.; Trombetta, John J.; Pillai, Meenu R.; Ratcliffe, Peter J.; Coleman, Mathew L.; Bix, Mark; Tantin, Dean; Park, Hongkun; Kuchroo, Vijay K.; Regev, Aviv

Note: Order does not necessarily reflect citation order of authors.

Citation: Yosef, N., A. K. Shalek, J. T. Gaublomme, H. Jin, Y. Lee, A. Awasthi, C. Wu, et al. 2013. “Dynamic regulatory network controlling Th17 cell differentiation.” Nature 496 (7446): 461-468. doi:10.1038/nature11981. http://dx.doi.org/10.1038/nature11981.
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Abstract: Despite their importance, the molecular circuits that control the differentiation of naïve 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 tools for performing perturbations in primary T cells to systematically derive and experimentally validate a model of the dynamic regulatory network that controls Th17 differentiation. The network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, whose coupled action may be essential for maintaining the balance between Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles, and highlights novel drug targets for controlling Th17 differentiation.
Published Version: doi:10.1038/nature11981
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637864/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878808
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