Dynamic regulatory network controlling TH 17 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: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2013
|
| _version_ | 1797059401804152832 |
|---|---|
| author | Yosef, N Shalek, A Gaublomme, J Jin, H Lee, Y Awasthi, A Wu, C Karwacz, K Xiao, S Jorgolli, M Gennert, D Satija, R Shakya, A Lu, D Trombetta, J Pillai, MR Ratcliffe, P Coleman, M Bix, M Tantin, D Park, H Kuchroo, V Regev, A |
| author_facet | Yosef, N Shalek, A Gaublomme, J Jin, H Lee, Y Awasthi, A Wu, C Karwacz, K Xiao, S Jorgolli, M Gennert, D Satija, R Shakya, A Lu, D Trombetta, J Pillai, MR Ratcliffe, P Coleman, M Bix, M Tantin, D Park, H Kuchroo, V Regev, A |
| author_sort | Yosef, N |
| collection | OXFORD |
| 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 TH 17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH 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 TH 17 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 TH 17 cell differentiation. © 2013 Macmillan Publishers Limited. All rights reserved. |
| first_indexed | 2024-03-06T20:03:43Z |
| format | Journal article |
| id | oxford-uuid:28378f21-8a16-46d1-ac69-a0637f2006f2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:03:43Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:28378f21-8a16-46d1-ac69-a0637f2006f22022-03-26T12:11:31ZDynamic regulatory network controlling TH 17 cell differentiationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:28378f21-8a16-46d1-ac69-a0637f2006f2EnglishSymplectic Elements at Oxford2013Yosef, NShalek, AGaublomme, JJin, HLee, YAwasthi, AWu, CKarwacz, KXiao, SJorgolli, MGennert, DSatija, RShakya, ALu, DTrombetta, JPillai, MRRatcliffe, PColeman, MBix, MTantin, DPark, HKuchroo, VRegev, ADespite 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 TH 17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH 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 TH 17 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 TH 17 cell differentiation. © 2013 Macmillan Publishers Limited. All rights reserved. |
| spellingShingle | Yosef, N Shalek, A Gaublomme, J Jin, H Lee, Y Awasthi, A Wu, C Karwacz, K Xiao, S Jorgolli, M Gennert, D Satija, R Shakya, A Lu, D Trombetta, J Pillai, MR Ratcliffe, P Coleman, M Bix, M Tantin, D Park, H Kuchroo, V Regev, A Dynamic regulatory network controlling TH 17 cell differentiation |
| title | Dynamic regulatory network controlling TH 17 cell differentiation |
| title_full | Dynamic regulatory network controlling TH 17 cell differentiation |
| title_fullStr | Dynamic regulatory network controlling TH 17 cell differentiation |
| title_full_unstemmed | Dynamic regulatory network controlling TH 17 cell differentiation |
| title_short | Dynamic regulatory network controlling TH 17 cell differentiation |
| title_sort | dynamic regulatory network controlling th 17 cell differentiation |
| work_keys_str_mv | AT yosefn dynamicregulatorynetworkcontrollingth17celldifferentiation AT shaleka dynamicregulatorynetworkcontrollingth17celldifferentiation AT gaublommej dynamicregulatorynetworkcontrollingth17celldifferentiation AT jinh dynamicregulatorynetworkcontrollingth17celldifferentiation AT leey dynamicregulatorynetworkcontrollingth17celldifferentiation AT awasthia dynamicregulatorynetworkcontrollingth17celldifferentiation AT wuc dynamicregulatorynetworkcontrollingth17celldifferentiation AT karwaczk dynamicregulatorynetworkcontrollingth17celldifferentiation AT xiaos dynamicregulatorynetworkcontrollingth17celldifferentiation AT jorgollim dynamicregulatorynetworkcontrollingth17celldifferentiation AT gennertd dynamicregulatorynetworkcontrollingth17celldifferentiation AT satijar dynamicregulatorynetworkcontrollingth17celldifferentiation AT shakyaa dynamicregulatorynetworkcontrollingth17celldifferentiation AT lud dynamicregulatorynetworkcontrollingth17celldifferentiation AT trombettaj dynamicregulatorynetworkcontrollingth17celldifferentiation AT pillaimr dynamicregulatorynetworkcontrollingth17celldifferentiation AT ratcliffep dynamicregulatorynetworkcontrollingth17celldifferentiation AT colemanm dynamicregulatorynetworkcontrollingth17celldifferentiation AT bixm dynamicregulatorynetworkcontrollingth17celldifferentiation AT tantind dynamicregulatorynetworkcontrollingth17celldifferentiation AT parkh dynamicregulatorynetworkcontrollingth17celldifferentiation AT kuchroov dynamicregulatorynetworkcontrollingth17celldifferentiation AT regeva dynamicregulatorynetworkcontrollingth17celldifferentiation |