Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches.

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 intrath

SUBMITTER: Martin-Gayo E 

PROVIDER: S-EPMC5679173 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature