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

作者：Buono Mario; Facchini Raffaella; Matsuoka Sahoko; Thongjuea Supat; Waithe Dominique; Luis Tiago C; Giustacchini Alice; Besmer Peter; Mead Adam J; Jacobsen Sten Eirik W^*; Nerlov Claus^*

来源：Nature Cell Biology, 2016, 18(2): 157-+.

DOI：10.1038/ncb3299

Thymic T cell development is initiated from bone-marrow-derived multi potent thymus-seeding progenitors. 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. Here we use the dependence of early, c-Kit-expressing thymic progenitors on Kit ligand (KitL) to show that CD4(-)CD8(-)c-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 CD4(-)CD8(-)c-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 change to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.

• 出版日期2016-2