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

• Published in: Nature cell biology Vol. 18; no. 2; pp. 157 - 167
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2016
• Subjects: Animals; Cell differentiation; Cell Differentiation - genetics; Cell Lineage; Cell Movement - genetics; Cells, Cultured; Coculture Techniques; Endothelial Cells - metabolism; Gene Expression Regulation, Developmental; Ligands; Lymphocytes; Medicin och hälsovetenskap; Mice, Transgenic; Multipotent Stem Cells - metabolism; Observations; Paracrine Communication - genetics; Phenotype; Properties; Signal Transduction; Stem Cell Factor - genetics; Stem Cell Factor - metabolism; Stem Cell Niche; Stem cells; T cells; Thymocytes - metabolism; Thymus gland; United Kingdom > UK; New York; United States > US
• ISSN: 1465-7392; 1476-4679; 1476-4679
• 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.