RBPJ-dependent Notch signaling initiates the T cell program in a subset of thymus-seeding progenitors
RBPJ-dependent Notch signaling initiates the T cell program in a subset of thymus-seeding progenitors
复制标题
DOI：
10.1038/s41590-019-0518-7
复制
发表时间：
2019-11-01
影响因子：
30.5
通讯作者：
Zuniga-Pflucker, Juan Carlos
中科院分区：
文献类型：
--
作者：
Chen, Edward L. Y.;Thompson, Patrycja K.;Zuniga-Pflucker, Juan Carlos
T细胞的特化和定型需要Notch信号传导。虽然在胸腺内T细胞发育过程中对Notch信号传导的需求是已知的，但仍不清楚T细胞引发的开始是否可以在胸腺前小生境中发生，以及RBPJ依赖性Notch信号传导是否在该事件中起作用。在这里，我们建立了一个Rbpj诱导系统，允许时间和组织特异性控制的反应，所有造血细胞中的Notch。使用这个系统，我们发现Notch信号在胸腺中的早期T细胞祖细胞阶段之前是必需的。骨髓中的类胸腺素致敏的多能祖细胞经历了具有Rbpj诱导的Notch信号传导，这抑制了胸腺接种祖细胞向骨髓谱系的发育。因此，我们的研究结果表明，T细胞分化的发病发生在前胸腺的设置，和Notch在此事件中发挥了重要作用。
T cell specification and commitment require Notch signaling. Although the requirement for Notch signaling during intrathymic T cell development is known, it is still unclear whether the onset of T cell priming can occur in a prethymic niche and whether RBPJ-dependent Notch signaling has a role during this event. Here, we established an Rbpj-inducible system that allowed temporal and tissue-specific control of the responsiveness to Notch in all hematopoietic cells. Using this system, we found that Notch signaling was required before the early T cell progenitor stage in the thymus. Lymphoid-primed multipotent progenitors in the bone marrow underwent Notch signaling with Rbpj induction, which inhibited development towards the myeloid lineage in thymus-seeding progenitors. Thus, our results indicated that the onset of T cell differentiation occurred in a prethymic setting, and that Notch played an important role during this event.