The interaction of the Wnt and Notch pathways modulates natural killer versus T cell differentiation
The interaction of the Wnt and Notch pathways modulates natural killer versus T cell differentiation
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DOI：
10.1634/stemcells.2007-0102
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Bernstein, Irwin D.
中科院分区：
文献类型：
--
作者：
Aoyama, Keisuke;Delaney, Colleen;Bernstein, Irwin D.
Wnt 和 Notch 信号通路已被独立证明在调节造血细胞命运决定中发挥关键作用。我们之前报道过，通过与Notch配体Delta1一起培养，在人CD34(+) CD38(-)脐带血细胞中诱导Notch信号传导，导致更多的细胞具有T或自然杀伤(NK)淋巴前体表型。在这里，我们发现，在Delta1中添加Wnt3a进一步增加了CD34(-) CD7(+)和CD34(-) CD7(+) cyCD3(+)细胞的百分比，同时CD3 epsilon和preT α的表达增加。相反，单独使用Wnt3a培养不会增加CD34(-)CD7(+)前体的产生或CD3ε或preTα基因的表达。此外，Wnt3a 增加了激活的 Notch1 的数量，表明 Wnt 通过影响 Notch 蛋白水平来调节 Notch 信号传导。相比之下，在 Delta1 中添加 Wnt 信号抑制剂则增加了 CD56(+) NK 细胞的百分比。总体而言，这些结果表明，Wnt 通路对 Notch 信号传导的调节在沿早期 T 或 NK 分化通路的前体细胞分化中发挥着关键作用。
The Wnt and Notch signaling pathways have been independently shown to play a critical role in regulating hematopoietic cell fate decisions. We previously reported that induction of Notch signaling in human CD34(+) CD38(-) cord blood cells by culture with the Notch ligand Delta1 resulted in more cells with T or natural killer ( NK) lymphoid precursor phenotype. Here, we show that addition of Wnt3a to Delta1 further increased the percentage of CD34(-) CD7(+) and CD34(-) CD7(+) cyCD3(+) cells with increased expression of CD3 epsilon and preT alpha. In contrast, culture with Wnt3a alone did not increase generation of CD34(-) CD7(+) precursors or expression of CD3 epsilon or preT alpha gene. Furthermore, Wnt3a increased the amount of activated Notch1, suggesting that Wnt modulates Notch signaling by affecting Notch protein levels. In contrast, addition of a Wnt signaling inhibitor to Delta1 increased the percentage of CD56(+) NK cells. Overall, these results demonstrate that regulation of Notch signaling by the Wnt pathway plays a critical role in differentiation of precursors along the early T or NK differentiation pathways.