P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development.
P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development.
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DOI：
10.1038/s41467-018-04167-y
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发表时间：
2018-05-02
影响因子：
16.6
通讯作者：
Rodríguez TA
中科院分区：
文献类型：
--
作者：
Bowling S;Di Gregorio A;Sancho M;Pozzi S;Aarts M;Signore M;D Schneider M;Martinez-Barbera JP;Gil J;Rodríguez TA
确保将有助于未来发育的多能细胞的适应性对于种系的完整性和正确的胚胎发生都是重要的。因此，越来越明显的是，多能细胞可以比较它们的适应性水平，并发出信号，淘汰那些比它们的邻居适应性差的细胞。在哺乳动物中，沟通适应性的途径的性质在很大程度上仍然未知。在这里，我们确定，在早期小鼠胚胎和退出幼稚多能性时，具有不同适应性水平的细胞的对抗导致在不太适合的细胞类型中抑制mTOR信号传导，导致其消除。我们发现，在这个过程中，p53作用于mTOR的上游，并需要抑制其活性。最后，我们证明了在正常发育过程中，大约35%的细胞被这一途径消除，突出了这一机制对胚胎发育的重要性。在胚胎发育过程中，细胞适应性决定了存活率，但这是如何调节的尚不清楚。在这里，作者表明，在早期胚胎发育和干细胞退出幼稚状态时，细胞感觉到它们的邻居的适应性，并触发p53抑制mTOR以消除三分之一的细胞。
Ensuring the fitness of the pluripotent cells that will contribute to future development is important both for the integrity of the germline and for proper embryogenesis. Consequently, it is becoming increasingly apparent that pluripotent cells can compare their fitness levels and signal the elimination of those cells that are less fit than their neighbours. In mammals the nature of the pathways that communicate fitness remain largely unknown. Here we identify that in the early mouse embryo and upon exit from naive pluripotency, the confrontation of cells with different fitness levels leads to an inhibition of mTOR signalling in the less fit cell type, causing its elimination. We show that during this process, p53 acts upstream of mTOR and is required to repress its activity. Finally, we demonstrate that during normal development around 35% of cells are eliminated by this pathway, highlighting the importance of this mechanism for embryonic development. During embryo development, cell fitness determines survival but how this is regulated is unclear. Here, the authors show that in early embryonic development and stem cells exiting the naive state, cells sense the fitness of their neighbours and trigger p53 to repress mTOR to eliminate a third of cells.
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影响因子：
1.5
作者：
Fu, Cary;Ess, Kevin C.
通讯作者：
Ess, Kevin C.
影响因子：
64.8
作者：
Bulut-Karslioglu, Aydan;Biechele, Steffen;Jin, Hu;Macrae, Trisha A.;Hejna, Miroslav;Gertsenstein, Marina;Song, Jun S.;Ramalho-Santos, Miguel
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作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
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作者：
Bondar T;Medzhitov R
通讯作者：
Medzhitov R