Martin-Gayo, EnriqueGonzález-García, SaraGarcía-León, María J.Murcia-Ceballos, AlbaAlcain, JuanGarcía-Peydró, MarinaAllende, LuisAndres, Belen deGaspar, Maria LuisaToribio, Maria L2019-02-072019-02-072017-08J Exp Med. 2017;6;214(11):3361-3379.0022-1007http://hdl.handle.net/20.500.12105/7144A 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.engVoRCell DedifferentiationCell LineageCells, CulturedDendritic CellsGATA2 Transcription FactorGene ExpressionHumansAttribution-NonCommercial-Share Alike 4.0 Internacional2894761221411337910.1084/jem.201615641540-9538The Journal of Experimental Medicineopen access