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Article: T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling

TitleT-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling
Authors
Issue Date2011
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 50, p. 20060-20065 How to Cite?
AbstractAlthough transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA-binding protein T-cell factor 1 (Tcf-1), a T-cell-specific mediator of Wnt signaling. However, the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate and show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of T-cell determination for progression beyond the early thymic progenitor stage. The global expression profile of Tcf-1-deficient progenitors indicates that basic processes of DNA metabolism are down-regulated in its absence, and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development.
Persistent Identifierhttp://hdl.handle.net/10722/180751
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGermar, Ken_US
dc.contributor.authorDose, Men_US
dc.contributor.authorKonstantinou, Ten_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorLobry, Cen_US
dc.contributor.authorArnett, KLen_US
dc.contributor.authorBlacklow, SCen_US
dc.contributor.authorAifantis, Ien_US
dc.contributor.authorAster, JCen_US
dc.contributor.authorGounari, Fen_US
dc.date.accessioned2013-01-28T01:42:17Z-
dc.date.available2013-01-28T01:42:17Z-
dc.date.issued2011en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 50, p. 20060-20065en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/180751-
dc.description.abstractAlthough transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA-binding protein T-cell factor 1 (Tcf-1), a T-cell-specific mediator of Wnt signaling. However, the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate and show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of T-cell determination for progression beyond the early thymic progenitor stage. The global expression profile of Tcf-1-deficient progenitors indicates that basic processes of DNA metabolism are down-regulated in its absence, and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBone Marrow Cells - Cytologyen_US
dc.subject.meshCell Lineage - Immunologyen_US
dc.subject.meshCell Movementen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshProto-Oncogene Proteins C-Kit - Metabolismen_US
dc.subject.meshReceptors, Notchen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshStem Cells - Cytologyen_US
dc.subject.meshT Cell Transcription Factor 1 - Deficiency - Metabolismen_US
dc.subject.meshT-Lymphocytes - Cytology - Immunologyen_US
dc.subject.meshThymocytes - Cytology - Immunologyen_US
dc.titleT-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signalingen_US
dc.typeArticleen_US
dc.identifier.emailZhang, J: jzhang1@hku.hken_US
dc.identifier.authorityZhang, J=rp01713en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.1110230108en_US
dc.identifier.pmid22109558en_US
dc.identifier.scopuseid_2-s2.0-84055178955en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84055178955&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume108en_US
dc.identifier.issue50en_US
dc.identifier.spage20060en_US
dc.identifier.epage20065en_US
dc.identifier.isiWOS:000298034800048-
dc.publisher.placeUnited Statesen_US
dc.identifier.f100013434971-
dc.identifier.scopusauthoridGermar, K=34976671500en_US
dc.identifier.scopusauthoridDose, M=8548572200en_US
dc.identifier.scopusauthoridKonstantinou, T=26428190900en_US
dc.identifier.scopusauthoridZhang, J=22137260600en_US
dc.identifier.scopusauthoridWang, H=36090312500en_US
dc.identifier.scopusauthoridLobry, C=15832471600en_US
dc.identifier.scopusauthoridArnett, KL=35508958100en_US
dc.identifier.scopusauthoridBlacklow, SC=7004227381en_US
dc.identifier.scopusauthoridAifantis, I=6603005523en_US
dc.identifier.scopusauthoridAster, JC=7005904242en_US
dc.identifier.scopusauthoridGounari, F=6603925154en_US

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