Epithelial-mesenchymal transition (EMT) is an instance of cellular plasticity that plays critical roles in development, regeneration and cancer progression. Recent studies indicate that the transition between epithelial and mesenchymal states is a multi-step and reversible process in which several intermediate phenotypes might coexist. These intermediate states correspond to various forms of stem-like cells in the EMT system, but the function of the multi-step transition or the multiple stem cell phenotypes is unclear. Here, we use mathematical models to show that multiple intermediate phenotypes in the EMT system help to attenuate the overall fluctuations of the cell population in terms of phenotypic compositions, thereby stabilizing a heterogeneous cell population in the EMT spectrum. We found that the ability of the system to attenuate noise on the intermediate states depends on the number of intermediate states, indicating the stem-cell population is more stable when it has more sub-states. Our study reveals a novel advantage of multiple intermediate EMT phenotypes in terms of systems design, and it sheds light on the general design principle of heterogeneous stem cell population.

中文翻译：

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通过多个中间细胞状态控制上皮-间质转化中的随机性。

上皮-间质转化（EMT）是细胞可塑性的一个实例，在发育，再生和癌症进展中起着至关重要的作用。最近的研究表明，上皮状态和间质状态之间的转换是一个多步骤且可逆的过程，其中可能存在多种中间表型。这些中间状态对应于EMT系统中各种形式的干样细胞，但不清楚多步过渡或多种干细胞表型的功能。在这里，我们使用数学模型来显示EMT系统中的多个中间表型有助于减弱表型组成方面的总体细胞波动，从而稳定EMT谱中的异质细胞群体。我们发现系统减弱中间状态噪声的能力取决于中间状态的数量，这表明当具有更多的子状态时，干细胞群体会更稳定。我们的研究揭示了多种中间EMT表型在系统设计方面的新颖优势，并阐明了异种干细胞群体的一般设计原理。