Dynamic regulatory network controlling TH17 cell differentiation
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/80821 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1811078207886065664 |
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| author | Yosef, Nir Shalek, Alex K. Gaublomme, Jellert T. Jin, Hulin Lee, Youjin Awasthi, Amit Wu, Chuan Karwacz, Katarzyna Xiao, Sheng Jorgolli, Marsela Gennert, David Satija, Rahul Shakya, Arvind Trombetta, John J. Pillai, Meenu R. Ratcliffe, Peter J. Coleman, Mathew L. Bix, Mark Tantin, Dean Park, Hongkun Kuchroo, Vijay K. Regev, Aviv Lu, Diana |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yosef, Nir Shalek, Alex K. Gaublomme, Jellert T. Jin, Hulin Lee, Youjin Awasthi, Amit Wu, Chuan Karwacz, Katarzyna Xiao, Sheng Jorgolli, Marsela Gennert, David Satija, Rahul Shakya, Arvind Trombetta, John J. Pillai, Meenu R. Ratcliffe, Peter J. Coleman, Mathew L. Bix, Mark Tantin, Dean Park, Hongkun Kuchroo, Vijay K. Regev, Aviv Lu, Diana |
| author_sort | Yosef, Nir |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:55:38Z |
| format | Article |
| id | mit-1721.1/80821 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:55:38Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/808212022-09-27T15:57:05Z Dynamic regulatory network controlling TH17 cell differentiation Dynamic regulatory network controlling T[subscript H]17 cell differentiation Yosef, Nir Shalek, Alex K. Gaublomme, Jellert T. Jin, Hulin Lee, Youjin Awasthi, Amit Wu, Chuan Karwacz, Katarzyna Xiao, Sheng Jorgolli, Marsela Gennert, David Satija, Rahul Shakya, Arvind Trombetta, John J. Pillai, Meenu R. Ratcliffe, Peter J. Coleman, Mathew L. Bix, Mark Tantin, Dean Park, Hongkun Kuchroo, Vijay K. Regev, Aviv Lu, Diana Massachusetts Institute of Technology. Department of Biology Regev, Aviv Lu, Diana Regev, Aviv 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. National Human Genome Research Institute (U.S.) (1P50HG006193-01) National Institutes of Health (U.S.). Pioneer Award (DP1OD003958-01) Howard Hughes Medical Institute Klarman Cell Observatory 2013-09-20T13:50:01Z 2013-09-20T13:50:01Z 2013-03 2012-09 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/80821 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. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1038/nature11981 Nature 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. application/pdf Nature Publishing Group Regev via Courtney Crummett |
| spellingShingle | Yosef, Nir Shalek, Alex K. Gaublomme, Jellert T. Jin, Hulin Lee, Youjin Awasthi, Amit Wu, Chuan Karwacz, Katarzyna Xiao, Sheng Jorgolli, Marsela Gennert, David Satija, Rahul Shakya, Arvind Trombetta, John J. Pillai, Meenu R. Ratcliffe, Peter J. Coleman, Mathew L. Bix, Mark Tantin, Dean Park, Hongkun Kuchroo, Vijay K. Regev, Aviv Lu, Diana Dynamic regulatory network controlling TH17 cell differentiation |
| title | Dynamic regulatory network controlling TH17 cell differentiation |
| title_full | Dynamic regulatory network controlling TH17 cell differentiation |
| title_fullStr | Dynamic regulatory network controlling TH17 cell differentiation |
| title_full_unstemmed | Dynamic regulatory network controlling TH17 cell differentiation |
| title_short | Dynamic regulatory network controlling TH17 cell differentiation |
| title_sort | dynamic regulatory network controlling th17 cell differentiation |
| url | http://hdl.handle.net/1721.1/80821 https://orcid.org/0000-0001-8567-2049 |
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