A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
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DOI：
10.1038/ncb3299
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发表时间：
2016-02
影响因子：
21.3
通讯作者：
Nerlov C
中科院分区：
文献类型：
--
作者：
Buono M;Facchini R;Matsuoka S;Thongjuea S;Waithe D;Luis TC;Giustacchini A;Besmer P;Mead AJ;Jacobsen SE;Nerlov C
胸腺T细胞发育起始于骨髓来源的多能胸腺接种祖细胞（TSP）。在胸腺细胞分化的早期阶段，祖细胞变得T细胞受限。然而，支持胸腺皮质内T细胞发育的这些关键初始阶段的细胞环境尚不清楚。我们在此使用早期表达c-Kit的胸腺祖细胞对Kit配体（KitL）的依赖性来表明，CD 4-CD 8-c-Kit+ CD 25-DN 1阶段祖细胞与皮质特异性表达KitL的血管内皮细胞（VEC）群体提供的膜结合形式KitL（mKitL）相关并依赖于此。相反，随后的CD 4-CD 8-c-Kit+ CD 25 + DN 2阶段祖细胞选择性地与皮质胸腺上皮细胞（cTEC）结合，并依赖于cTEC呈递的mKitL。这些结果表明，早期胸腺祖细胞分化的动态过程是由迁移依赖性的变化，支持生态位，并确定血管内皮细胞作为胸腺生态位细胞，与mKitL作为一个关键的配体。
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 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 changes to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.