Dynamic regulatory network controlling TH17 cell differentiation
Name
Yosef Final_manuscript with figures and supp info.pdf
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7.4 MB
Format
Adobe PDF
Checksum (MD5)
5364c373baf39d8c04067a0d733fc031
Author(s)
Yosef, Nir
Shalek, Alex K.
Gaublomme, Jellert T.
Jin, Hulin
Lee, Youjin
Awasthi, Amit
Wu, Chuan
Karwacz, Katarzyna
Xiao, Sheng
Jorgolli, Marsela
Alternative Title
Dynamic regulatory network controlling T[subscript H]17 cell differentiation
Date Issued
March 2013
Journal
Nature
Publisher
Nature Publishing Group
Citation
Yosef, Nir, Alex K. Shalek, Jellert T. Gaublomme, Hulin Jin, Youjin Lee, Amit Awasthi, Chuan Wu, et al. “Dynamic regulatory network controlling TH17 cell differentiation.” Nature 496, no. 7446 (March 6, 2013): 461-468.
Version
Author's final manuscript
Abstract
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[subscript H]17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The T[subscript 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[subscript H]17 and other CD4[superscript +] 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[subscript H]17 cell differentiation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nature11981
