Dynamic regulatory network controlling Th17 cell differentiation
View/ Open
Author
Shalek, Alex K.
Jin, Hulin
Awasthi, Amit
Xiao, Sheng
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
Regev, Aviv
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nature11981Metadata
Show full item recordCitation
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.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.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#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878808
Collections
- FAS Scholarly Articles [18256]
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)