Cell competition, the kinetics of thymopoiesis and thymus cellularity are regulated by double negative 2 to 3 early thymocytes
Cell competition, the kinetics of thymopoiesis and thymus cellularity are regulated by double negative 2 to 3 early thymocytes
复制标题
细胞竞争、胸腺生成动力学和胸腺细胞结构受双阴性 2 至 3 个早期胸腺细胞的调节
DOI：
10.1101/2019.12.21.885673
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Vera C. Martins
中科院分区：
文献类型：
--
作者：
Camila V. Ramos;Luna Ballesteros;J. Silva;Rafael A. Paiva;Marta F. Nogueira;J. Carneiro;Erida Gjini;Vera C. Martins
胸腺内的细胞竞争是一个自我平衡的过程，它驱动着细胞的更替。如果这一过程受损，胸腺功能可以自主维持数周，但这会导致白血病。我们的目的是了解细胞竞争对胸腺生成的影响，识别参与的细胞，并确定这一过程是如何被调节的。通过胸腺移植实验，我们发现细胞竞争发生在双阴性2 （DN2）和3早期（DN3e）胸腺细胞内，抑制了胸腺的自主性。此外，DN2b的扩增受到双阳性胸腺细胞施加的负反馈回路的调节，并决定了胸腺生成的动力学。在白介素7可用性控制的反应中，这种反馈回路影响DN2b的细胞周期持续时间。总之，我们表明，胸腺细胞不只是遵循预先确定的路径，如果提供正确的信号。相反，胸腺发育动态地整合了细胞自主和非细胞自主的方面，微调正常的胸腺功能。
Cell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the impact of cell competition on thymopoiesis, identify the cells involved and determine how the process is regulated. Using thymus transplantation experiments we found that cell competition occurs within the double negative 2 (DN2) and 3 early (DN3e) thymocytes and inhibits thymus autonomy. Furthermore, the expansion of DN2b is regulated by a negative feedback loop imposed by double positive thymocytes and determines the kinetics of thymopoiesis. This feedback loop impacts on cell cycle duration of DN2b, in a response controlled by interleukin 7 availability. Altogether, we show that thymocytes do not merely follow a pre-determined path if provided with the correct signals. Instead, thymopoiesis dynamically integrates cell autonomous and non-cell autonomous aspects that fine-tune normal thymus function.
影响因子：
64.8
作者：
Martins, Vera C.;Busch, Katrin;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
20.3
作者：
Liu, Cunlan;Saito, Fumi;Takahama, Yousuke
通讯作者：
Takahama, Yousuke
影响因子：
20.3
作者：
Zlotoff, Daniel A.;Sambandam, Arivazhagan;Bhandoola, Avinash
通讯作者：
Bhandoola, Avinash