2026-06-14T03:31:46Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. 7 Programa Marco
2019-02-07T14:06:02Z
2019-02-07T14:06:02Z
2017-08
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
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.
eng
Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches
journal article
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PMC5679173_SpatiallyRestrictedJAG1-Notch_2017.pdf
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PMC5679173_SpatiallyRestrictedJAG1-Notch_2017.pdf.txt