Martín Gayo, EnriqueGonzález García, SaraGarcía León, María J.Murcia Ceballos, AlbaAlcain, JuanGarcía Peydró, MarinaAllende Martínez, Luis MiguelDe Andrés, BelénGaspar, María L.Toribio, María L.2025-01-232025-01-232017-09-25Martín-Gayo E, González-García S, García-León MJ, Murcia-Ceballos A, Alcain J, García-Peydró M, Allende L, de Andrés B, Gaspar ML, Toribio ML. Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches. J Exp Med. 2017 Nov 6;214(11):3361-3379. doi: 10.1084/jem.20161564.0022-100710.1084/jem.20161564https://hdl.handle.net/20.500.14352/115701A 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.engAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/journal article1540-9538https://doi.org/10.1084/jem.2016156428947612https://rupress.org/jem/article/214/11/3361/42271/Spatially-restricted-JAG1-Notch-signaling-in-humanhttps://pubmed.ncbi.nlm.nih.gov/28947612/open access612.017HematopoiesisCiencias BiomédicasMedicinaInmunología32 Ciencias Médicas