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Please use this identifier to cite or link to this item: http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4960
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dc.contributorMinisterio de Economía y Competitividad (España)-
dc.contributorComunidad de Madrid-
dc.contributorObra Social la Caixa-
dc.contributorFundación Eugenio Rodríguez Pascual-
dc.contributorFundación Ramón Areces-
dc.creatorGarcía-Peydró, Marina-
dc.creatorYébenes, Virginia G. de-
dc.creatorToribio, María Luisa-
dc.date2008-06-10T14:26:53Z-
dc.date2008-06-10T14:26:53Z-
dc.date2006-
dc.date.accessioned2017-01-31T01:38:43Z-
dc.date.available2017-01-31T01:38:43Z-
dc.identifierThe Journal of Immunology, 2006, 177: 3711-3720-
dc.identifier0022-1767 (Print)-
dc.identifier1550-6606 (Online)-
dc.identifierhttp://hdl.handle.net/10261/4960-
dc.identifier.urihttp://dspace.mediu.edu.my:8181/xmlui/handle/10261/4960-
dc.descriptionArticle available at http://www.jimmunol.org/cgi/content/abstract/177/6/3711-
dc.descriptionNotch signaling is critical for T cell development of multipotent hemopoietic progenitors. Yet, how Notch regulates T cell fate specification during early thymopoiesis remains unclear. In this study, we have identified an early subset of CD34highc-kit+flt3+IL-7R+ cells in the human postnatal thymus, which includes primitive progenitors with combined lymphomyeloid potential. To assess the impact of Notch signaling in early T cell development, we expressed constitutively active Notch1 in such thymic lymphomyeloid precursors (TLMPs), or triggered their endogenous Notch pathway in the OP9-Delta-like1 stroma coculture. Our results show that proliferation vs differentiation is a critical decision influenced by Notch at the TLMP stage. We found that Notch signaling plays a prominent role in inhibiting non-T cell differentiation (i.e., macrophages, dendritic cells, and NK cells) of TLMPs, while sustaining the proliferation of undifferentiated thymocytes with T cell potential in response to unique IL-7 signals. However, Notch activation is not sufficient for inducing T-lineage progression of proliferating progenitors. Rather, stroma-derived signals are concurrently required. Moreover, while ectopic IL-7R expression cannot replace Notch for the maintenance and expansion of undifferentiated thymocytes, Notch signals sustain IL-7R expression in proliferating thymocytes and induce IL-7R up-regulation in a T cell line. Thus, IL-7R and Notch pathways cooperate to synchronize cell proliferation and suppression of non-T lineage choices in primitive intrathymic progenitors, which will be allowed to progress along the T cell pathway only upon interaction with an inductive stromal microenvironment. These data provide insight into a mechanism of Notch-regulated amplification of the intrathymic pool of early human T cell progenitors-
dc.descriptionThis work was supported by grants from Plan Nacional de Biomedicina (SAF2004-01122 and GEN2003-20649-C06-02), Comunidad de Madrid (GR/SAL/0143/ 2004), Fundación La Caixa (ON03/109-00), and Fundación Eugenio Rodríguez Pascual. We thank the Fundación Ramón Areces for an institutional grant to the Centro de Biología Molecular Severo Ochoa-
dc.descriptionPeer reviewed-
dc.format664838 bytes-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherAmerican Association of Immunologists-
dc.rightsopenAccess-
dc.subjectHuman-
dc.subjectT cells-
dc.subjectCell proliferation-
dc.subjectHematopoiesis-
dc.subjectThymus-
dc.titleNotch1 and IL-7 Receptor Interplay Maintains Proliferation of Human Thymic Progenitors while Suppressing Non-T Cell Fates-
dc.typeArtículo-
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