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dc.contributor.author | Martin-Gayo, Enrique | |
dc.contributor.author | González-García, Sara | |
dc.contributor.author | García-León, María J. | |
dc.contributor.author | Murcia-Ceballos, Alba | |
dc.contributor.author | Alcain, Juan | |
dc.contributor.author | García-Peydró, Marina | |
dc.contributor.author | Allende, Luis | |
dc.contributor.author | Andres, Belen de | |
dc.contributor.author | Gaspar, Maria Luisa | |
dc.contributor.author | Toribio, Maria L | |
dc.date.accessioned | 2019-02-07T14:06:02Z | |
dc.date.available | 2019-02-07T14:06:02Z | |
dc.date.issued | 2017-08 | |
dc.identifier.citation | J Exp Med. 2017;6;214(11):3361-3379. | es_ES |
dc.identifier.issn | 0022-1007 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7144 | |
dc.description.abstract | A 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Rockefeller University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Cell Dedifferentiation | es_ES |
dc.subject.mesh | Cell Lineage | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Dendritic Cells | es_ES |
dc.subject.mesh | GATA2 Transcription Factor | es_ES |
dc.subject.mesh | Gene Expression | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Intercellular Signaling Peptides and Proteins | es_ES |
dc.subject.mesh | Interleukin-3 Receptor alpha Subunit | es_ES |
dc.subject.mesh | Jagged-1 Protein | es_ES |
dc.subject.mesh | Membrane Proteins | es_ES |
dc.subject.mesh | Microscopy, Confocal | es_ES |
dc.subject.mesh | Monocytes | es_ES |
dc.subject.mesh | Myeloid Cells | es_ES |
dc.subject.mesh | Receptors, Notch | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.subject.mesh | Thymus Gland | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Stem Cell Niche | es_ES |
dc.title | Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-Share Alike 4.0 Internacional | * |
dc.identifier.pubmedID | 28947612 | es_ES |
dc.format.volume | 214 | es_ES |
dc.format.number | 11 | es_ES |
dc.format.page | 3379 | es_ES |
dc.identifier.doi | 10.1084/jem.20161564 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Comisión Europea. 7 Programa Marco | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1540-9538 | es_ES |
dc.relation.publisherversion | https://www.doi.org/10.1084/jem.20161564 | es_ES |
dc.identifier.journal | The Journal of Experimental Medicine | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-44857-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-75442-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RTI CC RD06/0014/1012 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/602587 | es_ES |
dc.rights.accessRights | open access | es_ES |