Notch signaling is necessary for GATA3 function in the initiation of T cell development
Notch signaling is necessary for GATA3 function in the initiation of T cell development
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DOI：
10.1002/eji.200737688
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Habu, Sonoko
中科院分区：
文献类型：
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作者：
Hozumi, Katsuto;Negishi, Naoko;Habu, Sonoko
GATA 3和Notch 1在T细胞发育的最早阶段是必不可少的，但它们在这一过程中的相互作用仍有待澄清。在这项研究中，我们证明了在妊娠第11.5天（E11.5）的GATA 3缺陷胎肝（FL）的造血祖细胞（HPC）中T淋巴细胞生成的损伤仅通过引入GATA 3和Notch 1的细胞内区域而不是单独引入来挽救。然而，仅引入GATA3足以在晚期阶段在GATA3缺陷型FL细胞中诱导T细胞，其中Notch信号传导是可良好检测的。这表明Notch信号传导对于GATA 3发挥T细胞命运特化的功能是必需的，但在没有GATA 3的情况下是不够的。另一方面，Notch信号传导足以在没有GATA 3的情况下阻断B细胞发育，这表明分支点处的T细胞命运特化不是简单地由Notch信号传导引起的B细胞谱系的发育停滞引起的。
GATA3 and Notch1 are essential for T cell development at the earliest stage, but their mutual roles in this process remain to be clarified. In this study, we demonstrated that impairment of T lymphopoiesis in hematopoietic progenitor cells (HPC) of GATA3-deficient fetal liver (FL) on day 11.5 of gestation (E11.5) was rescued only by introduction of both GATA3 and the intracellular region of Notch1 but not by either alone. However, the introduction of GATA3 only was sufficient for T cell induction in GATA3-deficient FL cells at the advanced stage, where Notch signaling is well detectable. This indicates that Notch signaling is necessary for GATA3 to function for T cell fate specification but is not sufficient without GATA3. On the other hand, Notch signaling is sufficient for blockage of B cell development without GATA3, suggesting that T cell fate specification at the branching point does not result simply from the developmental arrest of B cell lineage by Notch signaling.