Author
Listed:
- Nir Yosef
(Broad Institute of MIT and Harvard, 7 Cambridge Center
Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Alex K. Shalek
(Harvard University)
- Jellert T. Gaublomme
(Harvard University)
- Hulin Jin
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Youjin Lee
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Amit Awasthi
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School
Present address: Translational Health Science & Technology Institute, Faridabad, Haryana 122016, India.)
- Chuan Wu
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Katarzyna Karwacz
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Sheng Xiao
(Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Marsela Jorgolli
(Harvard University)
- David Gennert
(Broad Institute of MIT and Harvard, 7 Cambridge Center)
- Rahul Satija
(Broad Institute of MIT and Harvard, 7 Cambridge Center)
- Arvind Shakya
(University of Utah School of Medicine)
- Diana Y. Lu
(Broad Institute of MIT and Harvard, 7 Cambridge Center)
- John J. Trombetta
(Broad Institute of MIT and Harvard, 7 Cambridge Center)
- Meenu R. Pillai
(St. Jude Children's Research Hospital)
- Peter J. Ratcliffe
(University of Oxford, Headington Campus, Oxford OX3 7BN, UK)
- Mathew L. Coleman
(University of Oxford, Headington Campus, Oxford OX3 7BN, UK)
- Mark Bix
(St. Jude Children's Research Hospital)
- Dean Tantin
(University of Utah School of Medicine)
- Hongkun Park
(Broad Institute of MIT and Harvard, 7 Cambridge Center
Harvard University)
- Vijay K. Kuchroo
(Broad Institute of MIT and Harvard, 7 Cambridge Center
Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School)
- Aviv Regev
(Broad Institute of MIT and Harvard, 7 Cambridge Center
Howard Hughes Medical Institute, Massachusetts Institute of Technology)
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.
Suggested Citation
Nir Yosef & Alex K. Shalek & Jellert T. Gaublomme & Hulin Jin & Youjin Lee & Amit Awasthi & Chuan Wu & Katarzyna Karwacz & Sheng Xiao & Marsela Jorgolli & David Gennert & Rahul Satija & Arvind Shakya , 2013.
"Dynamic regulatory network controlling TH17 cell differentiation,"
Nature, Nature, vol. 496(7446), pages 461-468, April.
Handle:
RePEc:nat:nature:v:496:y:2013:i:7446:d:10.1038_nature11981
DOI: 10.1038/nature11981
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Cited by:
- Hao Li & Zebei Han & Yu Sun & Fu Wang & Pengzhen Hu & Yuang Gao & Xuemei Bai & Shiyu Peng & Chao Ren & Xiang Xu & Zeyu Liu & Hebing Chen & Yang Yang & Xiaochen Bo, 2024.
"CGMega: explainable graph neural network framework with attention mechanisms for cancer gene module dissection,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
- Andrew McDavid & Lucas Dennis & Patrick Danaher & Greg Finak & Michael Krouse & Alice Wang & Philippa Webster & Joseph Beechem & Raphael Gottardo, 2014.
"Modeling Bi-modality Improves Characterization of Cell Cycle on Gene Expression in Single Cells,"
PLOS Computational Biology, Public Library of Science, vol. 10(7), pages 1-10, July.
- Amber Delmas & Angelos Oikonomopoulos & Precious N Lacey & Mohammad Fallahi & Daniel W Hommes & Mark S Sundrud, 2016.
"Informatics-Based Discovery of Disease-Associated Immune Profiles,"
PLOS ONE, Public Library of Science, vol. 11(9), pages 1-16, September.
- Anat Kreimer & Tal Ashuach & Fumitaka Inoue & Alex Khodaverdian & Chengyu Deng & Nir Yosef & Nadav Ahituv, 2022.
"Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation,"
Nature Communications, Nature, vol. 13(1), pages 1-15, December.
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