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Diversity and plasticity of Th cell types predicted from regulatory network modelling

2010-09-02Journal article Open access
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dc.contributor.authorNaldi, Aurélien
dc.contributor.authorCarneiro, Jorge
dc.contributor.authorChaouiya, Claudine
dc.contributor.authorThieffry, Denis
dc.date.accessioned2016-05-05T08:27:38Z
dc.date.available2016-05-05T08:27:38Z
dc.date.issued2010-09-02
dc.description.abstractAlternative cell differentiation pathways are believed to arise from the concerted action of signalling pathways and transcriptional regulatory networks. However, the prediction of mammalian cell differentiation from the knowledge of the presence of specific signals and transcriptional factors is still a daunting challenge. In this respect, the vertebrate hematopoietic system, with its many branching differentiation pathways and cell types, is a compelling case study. In this paper, we propose an integrated, comprehensive model of the regulatory network and signalling pathways controlling Th cell differentiation. As most available data are qualitative, we rely on a logical formalism to perform extensive dynamical analyses. To cope with the size and complexity of the resulting network, we use an original model reduction approach together with a stable state identification algorithm. To assess the effects of heterogeneous environments on Th cell differentiation, we have performed a systematic series of simulations considering various prototypic environments. Consequently, we have identified stable states corresponding to canonical Th1, Th2, Th17 and Treg subtypes, but these were found to coexist with other transient hybrid cell types that co-express combinations of Th1, Th2, Treg and Th17 markers in an environment-dependent fashion. In the process, our logical analysis highlights the nature of these cell types and their relationships with canonical Th subtypes. Finally, our logical model can be used to explore novel differentiation pathways in silico.pt_PT
dc.description.sponsorshipFrench National Agency projects: (ANR-06-BYOS-0006, ANR-08-SYSC-003); Belgian Science Policy Office (IAP BioMaGNet); Calouste Gulbenkian Foundation.pt_PT
dc.identifier.citationNaldi A, Carneiro J, Chaouiya C, Thieffry D (2010) Diversity and Plasticity of Th Cell Types Predicted from Regulatory Network Modelling. PLoS Comput Biol 6(9): e1000912. doi:10.1371/journal.pcbi.1000912pt_PT
dc.identifier.doi10.1371/journal.pcbi.1000912pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/595
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttp://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000912pt_PT
dc.subjectCytokinespt_PT
dc.subjectCell differentiationpt_PT
dc.subjectRegulatory T cellspt_PT
dc.subjectGraphspt_PT
dc.subjectTranscription factorspt_PT
dc.subjectT cellspt_PT
dc.subjectT cell receptorspt_PT
dc.subjectT helper cellspt_PT
dc.titleDiversity and plasticity of Th cell types predicted from regulatory network modellingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage16pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLOS Computational Biologypt_PT
oaire.citation.volume6pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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