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BIOMD0000000592 - Martinez-Sanchez2015 - T CD4+ lymphocyte transcriptional regulatory network

 

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Reference Publication
Publication ID: 26090929
Martinez-Sanchez ME, Mendoza L, Villarreal C, Alvarez-Buylla ER.
A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity.
PLoS Comput. Biol. 2015 Jun; 11(6): e1004324
Departamento de Ecología Funcional, Instituto de Ecología, Universidad Nacional Autónoma de México, Coyoacán, México Distrito Federal, México; Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Coyoacán, México Distrito Federal, México.  [more]
Model
Original Model: MartinezSanchez2014_TCD4Tr...
Submitter: Mariana Martinez-Sanchez
Submission ID: MODEL1411170000
Submission Date: 17 Nov 2014 17:55:45 UTC
Last Modification Date: 04 Oct 2017 14:14:09 UTC
Creation Date: 11 Feb 2016 11:31:17 UTC
Encoders:  Mariana Martinez-Sanchez
   Alastair Hume
set #1
bqbiol:hasTaxon Taxonomy Vertebrata
set #2
bqbiol:isVersionOf Gene Ontology cell differentiation
Notes
Martinez-Sanchez2015 - T CD4+ lymphocyte transcriptional regulatory network

This model is described in the article:

Martinez-Sanchez ME, Mendoza L, Villarreal C, Alvarez-Buylla ER.
PLoS Comput. Biol. 2015 Jun; 11(6): e1004324

Abstract:

CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-? and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core and the micro-environment. We discuss the broader use of this approach for other plastic systems and possible therapeutic interventions.

This model is hosted on BioModels Database and identified by: BIOMD0000000592.

To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 26090929 Submission Date: 17 Nov 2014 17:55:45 UTC Last Modification Date: 04 Oct 2017 14:14:09 UTC Creation Date: 11 Feb 2016 11:31:17 UTC
Mathematical expressions
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   Spatial dimensions: NaN  Compartment size: NaN
Representative curation result(s)
Representative curation result(s) of BIOMD0000000592

Curator's comment: (updated: 08 Mar 2016 15:30:46 GMT)

Picture shows attractors found by GinSIM. This corresponds to figure 2A in the paper. The model has 10 nodes but only 5 are shown in the paper. The picture shows 9 steady states but the paper only shows 5. The authors wished to make the figure simple in the paper.

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