Dynamic regulatory network controlling Th17 cell differentiation
Shalek, Alex K.
Lu, Diana Y.
Trombetta, John J.
Pillai, Meenu R.
Ratcliffe, Peter J.
Coleman, Mathew L.
Regev, AvivNote: Order does not necessarily reflect citation order of authors.
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CitationYosef, 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.
AbstractDespite 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11878808