Mutation of p53 increases the competitive ability of pluripotent stem cells.
Mutation of p53 increases the competitive ability of pluripotent stem cells.
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DOI：
10.1242/dev.202503
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发表时间：
2024-01-15
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影响因子：
--
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--
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在发育过程中，细胞分裂和细胞死亡的相对平衡决定了组织的生长速度。细胞竞争是一种健康质量控制机制，它通过消除比邻近细胞更不适合的活细胞来促进这种平衡。赋予细胞竞争优势的突变以及赢家和输家细胞之间相互作用的动态还不是很清楚。在这里，我们展示了缺乏肿瘤抑制基因p53的胚胎细胞是“超级竞争者”，它们通过直接诱导细胞凋亡来消除它们的野生型邻居。这种消除是上下文相关的，因为当细胞具有多能性时不会发生这种消除，它是由分化开始触发的。此外，通过结合数学模型和基于细胞的分析，我们表明野生型细胞的消除不是通过竞争空间或营养物质，而是通过依赖于局部细胞邻域的短期相互作用来调节的。这突出了当地细胞邻里以及该邻里内的竞争性相互作用对于调节早期胚胎发育期间的增殖的重要性。摘要：携带p53基因突变的多能细胞通过消除野生型细胞的凋亡而获得竞争性生长优势。
During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are ‘super-competitors’ that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development. Summary: Pluripotent cells with p53 mutations gain a competitive growth advantage via the apoptotic elimination of wild-type cells.
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影响因子：
20.8
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
通讯作者：
Rodriguez TA
影响因子：
64.5
作者：
Moreno, E;Basler, K
通讯作者：
Basler, K
DOI：
10.1038/s41576-020-0262-8
发表时间：
2020-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Baker NE
通讯作者：
Baker NE
DOI：
10.1126/science.1258236
发表时间：
2014-12-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Meyer SN;Amoyel M;Bergantiños C;de la Cova C;Schertel C;Basler K;Johnston LA
通讯作者：
Johnston LA
影响因子：
64.8
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
通讯作者：
Torres, Miguel