AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis
AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis
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DOI：
10.1182/blood-2006-04-019570
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发表时间：
2006-11-15
期刊：
影响因子：
20.3
通讯作者：
Chiba, Shigeru
中科院分区：
文献类型：
--
作者：
Nakagawa, Masahiro;Ichikawa, Motoshi;Chiba, Shigeru
Notch 1-RBP-J κ和转录因子Runx 1通路已被独立地证明是建立永久性造血所不可或缺的。重要的是，Runx 1的表达在Notch 1和Rbpsuh缺失小鼠的主动脉旁内脏-胸膜（P-Sp）区域下调。在这里，我们证明，Notch 1上调Runx 1的表达和Notch 1无效的P-Sp细胞的造血功能缺陷被成功地救出在OP 9培养系统中的逆转录病毒转移Runx 1。我们还表明，Hes 1，一个已知的效应Notch信号，加强Runx 1介导的反式激活。与最近在斑马鱼中的发现一起，Runx 1被假定为在整个脊椎动物造血发育中Notch信号传导的主要下游介质。我们的研究结果还表明，Notch信号可以调节Runx 1的表达和转录活性。
The Notch1-RBP-J kappa and the transcription factor Runx1 pathways have been independently shown to be indispensable for the establishment of definitive hematopoiesis. Importantly, expression of Runx1 is down-regulated in the para-aortic splanch-nopleural (P-Sp) region of Notch1- and Rbpsuh-null mice. Here we demonstrate that Notch1 up-regulates Runx1 expression and that the defective hematopoietic potential of Notch1-null P-Sp cells is successfully rescued in the OP9 culture system by retroviral transfer of Runx1. We also show that Hes1, a known effector of Notch signaling, potentiates Runx1-mediated transactivation. Together with the recent findings in zebrafish, Runx1 is postulated to be a cardinal down-stream mediator of Notch signaling in hematopoietic development throughout vertebrates. Our findings also suggest that Notch signaling may modulate both expression and transcriptional activity of Runx1.