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

Alternative 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 st...

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Autores principales:	Aurélien Naldi, Jorge Carneiro, Claudine Chaouiya, Denis Thieffry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/345597f0b6934d768974d39581c068f5
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spelling	oai:doaj.org-article:345597f0b6934d768974d39581c068f52021-11-18T05:49:20ZDiversity and plasticity of Th cell types predicted from regulatory network modelling.1553-734X1553-735810.1371/journal.pcbi.1000912https://doaj.org/article/345597f0b6934d768974d39581c068f52010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20824124/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Alternative 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.Aurélien NaldiJorge CarneiroClaudine ChaouiyaDenis ThieffryPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 9, p e1000912 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Aurélien Naldi Jorge Carneiro Claudine Chaouiya Denis Thieffry Diversity and plasticity of Th cell types predicted from regulatory network modelling.
description	Alternative 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.
format	article
author	Aurélien Naldi Jorge Carneiro Claudine Chaouiya Denis Thieffry
author_facet	Aurélien Naldi Jorge Carneiro Claudine Chaouiya Denis Thieffry
author_sort	Aurélien Naldi
title	Diversity and plasticity of Th cell types predicted from regulatory network modelling.
title_short	Diversity and plasticity of Th cell types predicted from regulatory network modelling.
title_full	Diversity and plasticity of Th cell types predicted from regulatory network modelling.
title_fullStr	Diversity and plasticity of Th cell types predicted from regulatory network modelling.
title_full_unstemmed	Diversity and plasticity of Th cell types predicted from regulatory network modelling.
title_sort	diversity and plasticity of th cell types predicted from regulatory network modelling.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/345597f0b6934d768974d39581c068f5
work_keys_str_mv	AT aureliennaldi diversityandplasticityofthcelltypespredictedfromregulatorynetworkmodelling AT jorgecarneiro diversityandplasticityofthcelltypespredictedfromregulatorynetworkmodelling AT claudinechaouiya diversityandplasticityofthcelltypespredictedfromregulatorynetworkmodelling AT denisthieffry diversityandplasticityofthcelltypespredictedfromregulatorynetworkmodelling
_version_	1718424778729062400

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

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