Rothenberg Ellen V
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Curr Opin Hematol. 2007 Jul;14(4):322-9. doi: 10.1097/MOH.0b013e3281de72a8.
Initiation of T lymphocyte development depends on balanced regulatory inputs from multiple essential transcription factors. This review highlights contributions of E2A, hematopoietic transcription factor PU.1, growth factor independence (Gfi)-1, T cell factor (TCF)-1, and Runx factors and their interactions with the Notch pathway to promote T cell development.
E2A and Runx family factors have been implicated in establishing competent precursors in which Notch signaling can induce the T cell program. An early role was also indicated for PU.1. Later PU.1 activities are antagonistic to pro-T cell factors, however, including E proteins, Myb, Gfi-1, and TCF-1. Diversion to a non-T lineage can be promoted by PU.1, CCAAT/enhancer binding protein, or even GATA and TCF, but these diversion mechanisms are blocked by Notch signaling. An emergent gene network summarizes the cross-regulatory relationships among these factors.
Entry into the T-cell pathway is controlled by a dynamic balance among essential regulatory factors that depend on Notch signaling not only to trigger initiation of the T-cell program but also to maintain the lineage fidelity of their collective action.
T淋巴细胞发育的起始依赖于多种关键转录因子的平衡调节输入。本综述重点介绍了E2A、造血转录因子PU.1、生长因子独立性（Gfi）-1、T细胞因子（TCF）-1和Runx因子的作用，以及它们与Notch信号通路相互作用以促进T细胞发育的过程。
E2A和Runx家族因子参与建立有能力的前体细胞，其中Notch信号可诱导T细胞程序。PU.1也被指出具有早期作用。然而，PU.1后期的活性与前T细胞因子拮抗，包括E蛋白、Myb、Gfi-1和TCF-1。PU.1、CCAAT/增强子结合蛋白，甚至GATA和TCF可促进细胞转向非T谱系，但这些转向机制被Notch信号阻断。一个新兴的基因网络总结了这些因子之间的交叉调节关系。
进入T细胞途径受关键调节因子之间动态平衡的控制，这些因子不仅依赖Notch信号来触发T细胞程序的启动，还依赖其维持集体作用的谱系保真度。
