Notch signaling is the dominant intercellular signaling input during the earliest stages of T cell development in the thymus. Although Notch1 is known to be indispensable, we show that it does not mediate all Notch signaling in precommitment stages: Notch2 initially works in parallel to promote early murine T cell development and antagonize other fates. Notch-regulated target genes before and after T lineage commitment change dynamically, and we show that this partially reflects shifts in genome-wide DNA binding by RBPJ, the transcription factor activated by complex formation with the Notch intracellular domain. Although Notch signaling and transcription factor PU.1 can activate some common targets in precommitment T progenitors, Notch signaling and PU.1 activity have functionally antagonistic effects on multiple targets, delineating separation of pro-T cells from alternative PU.1-dependent fates. These results define a distinct mechanism of Notch signal response that distinguishes the initial stages of murine T cell development.

中文翻译：

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Notch2 补充 Notch1，介导启动早期 T 细胞发育的诱导信号传导

Notch 信号传导是胸腺 T 细胞发育最早阶段的主要细胞间信号传导输入。尽管已知Notch1是不可或缺的，但我们发现它并不介导预承诺阶段的所有Notch信号传导：Notch2最初并行地促进早期小鼠T细胞发育并拮抗其他命运。Notch 调控的靶基因在 T 谱系定型前后发生动态变化，我们发现这部分反映了 RBPJ 与全基因组 DNA 结合的变化，RBPJ 是通过与 Notch 胞内结构域形成复合物而激活的转录因子。尽管Notch信号传导和转录因子PU.1可以激活前定型T祖细胞中的一些常见靶标，但Notch信号传导和PU.1活性对多个靶标具有功能性拮抗作用，描绘了前T细胞与PU.1依赖的替代命运的分离。这些结果定义了 Notch 信号响应的独特机制，可区分小鼠 T 细胞发育的初始阶段。