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oai:repisalud.isciii.es:20.500.12105/71442024-11-28T15:55:42Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16938

00925njm 22002777a 4500 dc Martin-Gayo, Enrique author González-García, Sara author García-León, María J. author Murcia-Ceballos, Alba author Alcain, Juan author García-Peydró, Marina author Allende, Luis author Andres, Belen de author Gaspar, Maria Luisa author Toribio, Maria L author 2017-08 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. J Exp Med. 2017;6;214(11):3361-3379. 10.1084/jem.20161564 1540-9538 0022-1007 The Journal of Experimental Medicine 28947612 http://hdl.handle.net/20.500.12105/7144 Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches