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dc.contributor.authorHong, Tianen_US
dc.contributor.authorXing, Jianhuaen_US
dc.contributor.authorLi, Liwuen_US
dc.contributor.authorTyson, John J.en_US
dc.date.accessioned2016-12-09T21:37:12Z
dc.date.available2016-12-09T21:37:12Z
dc.date.issued2012-06-14en_US
dc.identifier.citationBMC Systems Biology. 2012 Jun 14;6(1):66
dc.identifier.issn1752-0509en_US
dc.identifier.urihttp://hdl.handle.net/10919/73637
dc.description.abstractBackground CD4+ T cells have several subsets of functional phenotypes, which play critical yet diverse roles in the immune system. Pathogen-driven differentiation of these subsets of cells is often heterogeneous in terms of the induced phenotypic diversity. In vitro recapitulation of heterogeneous differentiation under homogeneous experimental conditions indicates some highly regulated mechanisms by which multiple phenotypes of CD4+ T cells can be generated from a single population of naïve CD4+ T cells. Therefore, conceptual understanding of induced heterogeneous differentiation will shed light on the mechanisms controlling the response of populations of CD4+ T cells under physiological conditions. Results We present a simple theoretical framework to show how heterogeneous differentiation in a two-master-regulator paradigm can be governed by a signaling network motif common to all subsets of CD4+ T cells. With this motif, a population of naïve CD4+ T cells can integrate the signals from their environment to generate a functionally diverse population with robust commitment of individual cells. Notably, two positive feedback loops in this network motif govern three bistable switches, which in turn, give rise to three types of heterogeneous differentiated states, depending upon particular combinations of input signals. We provide three prototype models illustrating how to use this framework to explain experimental observations and make specific testable predictions. Conclusions The process in which several types of T helper cells are generated simultaneously to mount complex immune responses upon pathogenic challenges can be highly regulated, and a simple signaling network motif can be responsible for generating all possible types of heterogeneous populations with respect to a pair of master regulators controlling CD4+ T cell differentiation. The framework provides a mathematical basis for understanding the decision-making mechanisms of CD4+ T cells, and it can be helpful for interpreting experimental results. Mathematical models based on the framework make specific testable predictions that may improve our understanding of this differentiation system.
dc.format.extent? - ? (17) page(s)en_US
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.publisherBiomed Central Ltden_US
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000308706100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en_US
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMathematical & Computational Biologyen_US
dc.subjectROR-GAMMA-Ten_US
dc.subjectT(H)17 CELLSen_US
dc.subjectTGF-BETAen_US
dc.subjectTH2 DIFFERENTIATIONen_US
dc.subjectLINEAGE-COMMITMENTen_US
dc.subjectPROGENITOR CELLSen_US
dc.subjectRETINOIC ACIDen_US
dc.subjectGENEen_US
dc.subjectCYTOKINEen_US
dc.subjectGATA-3en_US
dc.titleA simple theoretical framework for understanding heterogeneous differentiation of CD4(+) T cellsen_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.rights.holderTian Hong et al.; licensee BioMed Central Ltd.
dc.title.serialBMC SYSTEMS BIOLOGYen_US
dc.identifier.doihttps://doi.org/10.1186/1752-0509-6-66
dc.identifier.volume6en_US
dc.type.dcmitypeText
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Faculty of Health Sciences
pubs.organisational-group/Virginia Tech/Science
pubs.organisational-group/Virginia Tech/Science/Biological Sciences
pubs.organisational-group/Virginia Tech/Science/COS T&R Faculty
pubs.organisational-group/Virginia Tech/University Distinguished Professors


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Creative Commons Attribution 4.0 International (CC BY 4.0)
License: Creative Commons Attribution 4.0 International (CC BY 4.0)