한빛사논문
- 조회4,652
Abstract
Nir Yosef1,2*, Alex K. Shalek3*, Jellert T. Gaublomme3*,Hulin Jin2, Youjin Lee2, Amit Awasthi2†, ChuanWu2, Katarzyna Karwacz2, Sheng Xiao2, Marsela Jorgolli3, David Gennert1, Rahul Satija1, Arvind Shakya4, Diana Y. Lu1, John J. Trombetta1, Meenu R. Pillai5, Peter J. Ratcliffe6, Mathew L. Coleman6, Mark Bix5, Dean Tantin4, Hongkun Park1,3, Vijay K. Kuchroo1,2 & Aviv Regev1,7
1Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. 2Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 3Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA. 4Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 5Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA. 6University of Oxford, Headington Campus, Oxford OX3 7BN, UK. 7Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA.
†Present address: Translational Health Science & Technology Institute, Faridabad, Haryana 122016, India.
*These authors contributed equally to this work.
Correspondence to: Hongkun Park or Vijay K. Kuchroo or Aviv Regev
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 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.
논문정보
- Research article
- 2013년 03월 (BRIC 등록일 )
- 국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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