Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development.
Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development.
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DOI：
10.1038/s42255-021-00422-7
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发表时间：
2021-08
影响因子：
20.8
通讯作者：
Rodriguez TA
中科院分区：
文献类型：
--
作者：
Lima A;Lubatti G;Burgstaller J;Hu D;Green AP;Di Gregorio A;Zawadzki T;Pernaute B;Mahammadov E;Perez-Montero S;Dore M;Sanchez JM;Bowling S;Sancho M;Kolbe T;Karimi MM;Carling D;Jones N;Srinivas S;Scialdone A;Rodriguez TA
细胞竞争作为一种质量控制机制正在出现，它可以在从发育到成人的广泛环境中消除不合适的细胞。然而，通常通过细胞竞争消除的细胞的性质以及触发其消除的原因仍然知之甚少。在小鼠中，35%的上胚层细胞在原肠胚形成之前被消除。在这里，我们表明，在小鼠发育早期，线粒体缺陷的细胞被细胞竞争所淘汰。使用单细胞转录谱消除小鼠上胚层细胞，我们确定细胞竞争和线粒体缺陷的标志。我们继续证明，线粒体缺陷是常见的一系列不同的失败者细胞类型和操纵线粒体功能触发细胞竞争。在小鼠胚胎中，细胞竞争消除了mt-Rnr 1和mt-Rnr 2序列变化的细胞，即使线粒体DNA序列的非病理性变化也可以诱导细胞竞争。我们的研究结果表明，细胞竞争是一个净化选择，优化线粒体性能前原肠胚。
Cell competition is emerging as a quality control mechanism that eliminates unfit cells in a wide range of settings from development to the adult. However, the nature of the cells normally eliminated by cell competition and what triggers their elimination remains poorly understood. In mice, 35% of epiblast cells are eliminated prior to gastrulation. Here we show that cells with mitochondrial defects are eliminated by cell competition during early mouse development. Using single cell transcriptional profiling of eliminated mouse epiblast cells we identify hallmarks of cell competition and mitochondrial defects. We go on to demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function triggers cell competition. In the mouse embryo, cell competition eliminates cells with sequence changes in mt-Rnr1 and mt-Rnr2, and that even non-pathological changes in mitochondrial DNA sequence can induce cell competition. Our results suggest that cell competition is a purifying selection that optimises mitochondrial performance prior to gastrulation.
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影响因子：
56.9
作者：
Fan, Weiwei;Waymire, Katrina G.;Wallace, Douglas C.
通讯作者：
Wallace, Douglas C.
影响因子：
8.8
作者：
Burgstaller JP;Johnston IG;Jones NS;Albrechtová J;Kolbe T;Vogl C;Futschik A;Mayrhofer C;Klein D;Sabitzer S;Blattner M;Gülly C;Poulton J;Rülicke T;Piálek J;Steinborn R;Brem G
通讯作者：
Brem G
影响因子：
30.8
作者：
Freyer, Christoph;Cree, Lynsey M.;Mourier, Arnaud;Stewart, James B.;Koolmeister, Camilla;Milenkovic, Dusanka;Wai, Timothy;Floros, Vasileios I.;Hagstrom, Erik;Chatzidaki, Emmanouella E.;Wiesner, Rudolf J.;Samuels, David C.;Larsson, Nils-Goeran;Chinnery, Patrick F.
通讯作者：
Chinnery, Patrick F.
影响因子：
64.8
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
通讯作者：
Torres, Miguel
影响因子：
8.8
作者：
Cheng, Shangli;Pei, Yu;Deng, Qiaolin
通讯作者：
Deng, Qiaolin