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A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors

Buono, M., Facchini, R., Matsuoka, S. et al.

Thymic T-cell development is initiated from bone marrow-derived multi-potent thymus seeding progenitors (TSPs). During the early stages of thymocyte differentiation progenitors become T-cell restricted. However, the cellular environments supporting these critical initial stages of T-cell development within the thymic cortex are not known. We here use the dependence of early, c-Kit–expressing thymic progenitors on Kit ligand (KitL) to show that CD4CD8c-Kit+CD25 DN1-stage progenitors associate with, and depend on the membrane-bound form of KitL (mKitL) provided by, a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4CD8c-Kit+CD25+ DN2 stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent changes to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.

Citation

Buono, M., Facchini, R., Matsuoka, S. et al. "A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors" Nature Cell Biology (2016): 157–67