Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development.
Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development.
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DOI：
10.1083/jcb.202005093
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
Hosokawa H
中科院分区：
文献类型：
--
作者：
Romero-Wolf M;Shin B;Zhou W;Koizumi M;Rothenberg EV;Hosokawa H
Notch 1在启动胸腺祖细胞的T谱系程序中发挥着不可或缺的作用。这项研究定义了Notch靶基因的阶段特异性调控，并表明Notch 2还在早期T细胞发育中放大了诱导性和谱系限制性Notch信号。Notch信号是胸腺中T细胞发育的最早阶段期间的主要细胞间信号输入。虽然Notch 1是必不可少的，我们表明，它并不介导所有的Notch信号在precommitment阶段：Notch 2最初平行工作，以促进早期小鼠T细胞的发展和拮抗其他命运。Notch调节的靶基因前后T谱系承诺动态变化，我们表明，这部分反映了RBPJ，转录因子激活的复合物形成与Notch细胞内结构域的全基因组DNA结合的变化。虽然Notch信号传导和转录因子PU.1可以激活预定型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pro-T细胞与替代PU.1依赖性命运的分离。这些结果定义了区分鼠T细胞发育的初始阶段的Notch信号应答的独特机制。
Notch1 has an indispensable role in initiating the T lineage program from progenitors in the thymus. This study defines stage-specific regulation of Notch target genes and shows that Notch2 also amplifies inductive and lineage-restrictive Notch signals in early T cell development. 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.
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影响因子：
32.4
作者：
Hu G;Cui K;Fang D;Hirose S;Wang X;Wangsa D;Jin W;Ried T;Liu P;Zhu J;Rothenberg EV;Zhao K
通讯作者：
Zhao K
DOI：
10.1084/jem.20061442
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Besseyrias V;Fiorini E;Strobl LJ;Zimber-Strobl U;Dumortier A;Koch U;Arcangeli ML;Ezine S;Macdonald HR;Radtke F
通讯作者：
Radtke F
影响因子：
30.5
作者：
Hosokawa H;Romero-Wolf M;Yui MA;Ungerbäck J;Quiloan MLG;Matsumoto M;Nakayama KI;Tanaka T;Rothenberg EV
通讯作者：
Rothenberg EV
DOI：
10.1073/pnas.1110230108
发表时间：
2011-12-13
影响因子：
11.1
作者：
Germar, Kristine;Dose, Marei;Gounari, Fotini
通讯作者：
Gounari, Fotini
影响因子：
32.4
作者：
Feyerabend, Thorsten B.;Terszowski, Grzegorz;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer