Show simple item record

dc.contributor.authorHong, Tianen
dc.contributor.authorXing, Jianhuaen
dc.contributor.authorLi, Liwuen
dc.contributor.authorTyson, John J.en
dc.date.accessioned2016-12-09T21:37:12Zen
dc.date.available2016-12-09T21:37:12Zen
dc.date.issued2012-06-14en
dc.identifier.citationBMC Systems Biology. 2012 Jun 14;6(1):66en
dc.identifier.issn1752-0509en
dc.identifier.urihttp://hdl.handle.net/10919/73637en
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.en
dc.format.extent? - ? (17) page(s)en
dc.format.mimetypeapplication/pdfen
dc.languageEnglishen
dc.publisherBiomed Central Ltden
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
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMathematical & Computational Biologyen
dc.subjectROR-GAMMA-Ten
dc.subjectT(H)17 CELLSen
dc.subjectTGF-BETAen
dc.subjectTH2 DIFFERENTIATIONen
dc.subjectLINEAGE-COMMITMENTen
dc.subjectPROGENITOR CELLSen
dc.subjectRETINOIC ACIDen
dc.subjectGENEen
dc.subjectCYTOKINEen
dc.subjectGATA-3en
dc.titleA simple theoretical framework for understanding heterogeneous differentiation of CD4(+) T cellsen
dc.typeArticle - Refereeden
dc.description.versionPublished versionen
dc.rights.holderTian Hong et al.; licensee BioMed Central Ltd.en
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.title.serialBMC SYSTEMS BIOLOGYen
dc.identifier.doihttps://doi.org/10.1186/1752-0509-6-66en
dc.identifier.volume6en
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Distinguished Professorsen


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International