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dc.contributor.authorMartin-Gayo, Enrique
dc.contributor.authorGonzález-García, Sara
dc.contributor.authorGarcía-León, María J.
dc.contributor.authorMurcia-Ceballos, Alba
dc.contributor.authorAlcain, Juan
dc.contributor.authorGarcía-Peydró, Marina
dc.contributor.authorAllende, Luis
dc.contributor.authorAndres, Belen de 
dc.contributor.authorGaspar, Maria Luisa 
dc.contributor.authorToribio, Maria L
dc.date.accessioned2019-02-07T14:06:02Z
dc.date.available2019-02-07T14:06:02Z
dc.date.issued2017-08
dc.identifier.citationJ Exp Med. 2017;6;214(11):3361-3379.es_ES
dc.identifier.issn0022-1007es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7144
dc.description.abstractA key unsolved question regarding the developmental origin of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) resident in the steady-state thymus is whether early thymic progenitors (ETPs) could escape T cell fate constraints imposed normally by a Notch-inductive microenvironment and undergo DC development. By modeling DC generation in bulk and clonal cultures, we show here that Jagged1 (JAG1)-mediated Notch signaling allows human ETPs to undertake a myeloid transcriptional program, resulting in GATA2-dependent generation of CD34+ CD123+ progenitors with restricted pDC, cDC, and monocyte potential, whereas Delta-like1 signaling down-regulates GATA2 and impairs myeloid development. Progressive commitment to the DC lineage also occurs intrathymically, as myeloid-primed CD123+ monocyte/DC and common DC progenitors, equivalent to those previously identified in the bone marrow, are resident in the normal human thymus. The identification of a discrete JAG1+ thymic medullary niche enriched for DC-lineage cells expressing Notch receptors further validates the human thymus as a DC-poietic organ, which provides selective microenvironments permissive for DC development.es_ES
dc.description.sponsorshipThis work was supported by funds from Plan Nacional, Ministerio de Ciencia e Innovación grants SAF2013-44857-R and SAF2016-75442-R (Agencia Estatal de Investigación/European Regional Development Fund, European Union), Instituto de Salud Carlos III (RTI CC RD06/0014/1012), and the Seventh Framework Programme of the European Union (FP7-HEALTH-2013-INNOVATION-1-602587) to M.L. Toribio; by grant SAF2015-70880-R (Agencia Estatal de Investigación/European Regional Development Fund, European Union) to M.L. Gaspar; and by an Institutional Grant from Fundación Ramón Areces. M.J. García-León and A. Murcia-Ceballos were supported by Ministerio de Ciencia e Innovación.es_ES
dc.language.isoenges_ES
dc.publisherRockefeller University Press es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshCell Dedifferentiation es_ES
dc.subject.meshCell Lineage es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshDendritic Cells es_ES
dc.subject.meshGATA2 Transcription Factor es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshHumans es_ES
dc.subject.meshIntercellular Signaling Peptides and Proteins es_ES
dc.subject.meshInterleukin-3 Receptor alpha Subunit es_ES
dc.subject.meshJagged-1 Protein es_ES
dc.subject.meshMembrane Proteins es_ES
dc.subject.meshMicroscopy, Confocal es_ES
dc.subject.meshMonocytes es_ES
dc.subject.meshMyeloid Cells es_ES
dc.subject.meshReceptors, Notch es_ES
dc.subject.meshT-Lymphocytes es_ES
dc.subject.meshThymus Gland es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshStem Cell Niche es_ES
dc.titleSpatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental nicheses_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-Share Alike 4.0 Internacional*
dc.identifier.pubmedID28947612es_ES
dc.format.volume214es_ES
dc.format.number11es_ES
dc.format.page3379es_ES
dc.identifier.doi10.1084/jem.20161564es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Comisión Europea. 7 Programa Marco 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1540-9538es_ES
dc.relation.publisherversionhttps://www.doi.org/10.1084/jem.20161564es_ES
dc.identifier.journalThe Journal of Experimental Medicinees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-44857-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-75442-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RTI CC RD06/0014/1012es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/602587es_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-Share Alike 4.0 Internacional
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