Myc-driven endogenous cell competition in the early mammalian embryo
Myc-driven endogenous cell competition in the early mammalian embryo
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DOI：
10.1038/nature12389
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发表时间：
2013-08-01
期刊：
影响因子：
64.8
通讯作者：
Torres, Miguel
中科院分区：
文献类型：
--
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
上胚层是哺乳动物的胚胎组织，其中包含能产生整个胚胎的多能干细胞。我们已经建立了一种在小鼠中诱导功能性基因嵌合体的方法。利用该系统，我们在此表明，在上胚层中诱导Myc表达的嵌合失衡，会通过凋亡消除Myc水平较低的细胞，促使Myc水平较高的细胞扩增，而不影响发育。相比之下，Myc水平的均匀变化并不影响上胚层细胞的生存能力，这表明观察到的竞争是由上胚层细胞之间相对Myc水平的比较导致的。在正常发育过程中，我们发现上胚层细胞之间的Myc水平本质上是异质的，并且内源性细胞竞争通过消除相对Myc水平较低的细胞来优化上胚层细胞群体。这些结果表明，哺乳动物早期胚胎中的自然细胞竞争有助于上胚层细胞库的选择。
The epiblast is the mammalian embryonic tissue that contains the pluripotent stem cells that generate the whole embryo. We have established a method for inducing functional genetic mosaics in the mouse. Using this system, here we show that induction of a mosaic imbalance of Myc expression in the epiblast provokes the expansion of cells with higher Myc levels through the apoptotic elimination of cells with lower levels, without disrupting development. In contrast, homogeneous shifts in Myc levels did not affect epiblast cell viability, indicating that the observed competition results from comparison of relative Myc levels between epiblast cells. During normal development we found that Myc levels are intrinsically heterogeneous among epiblast cells, and that endogenous cell competition refines the epiblast cell population through the elimination of cells with low relative Myc levels. These results show that natural cell competition in the early mammalian embryo contributes to the selection of the epiblast cell pool.