Phenotypic variability of growing cellular populations
Phenotypic variability of growing cellular populations
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DOI：
10.1073/pnas.0706115104
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发表时间：
2007-11-27
影响因子：
11.1
通讯作者：
Hasty, Jeff
中科院分区：
文献类型：
--
作者：
Lu, Ting;Shen, Tongye;Hasty, Jeff
增殖细胞群体的动态和多样性受群体内各种表型之间的生长率和死亡率之间的相互作用控制。此外，表观遗传多稳定性可以导致细胞自发地从一种表型转变为另一种表型。通过检查群体相对方差的广义形式并将其分类为群体内和群体间贡献，我们研究了细胞群体变异性的起源和后果。我们发现，变异性很大程度上取决于初始条件和增长环境对人口的限制。我们构建了一个双表型模型系统，并通过分析和数值方法检查了其在无限和人口有限的生长环境中的时间依赖性变异性。我们发现，在无限增长环境中，整体变异性严格受初始条件控制。相反，当总体人口受到环境限制时，无论初始条件如何，系统最终都会松弛到唯一的固定点。然而，到固定点的瞬态衰减很大程度上取决于初始条件，并且可变性衰减的时间尺度可能非常长，具体取决于系统的固有时间尺度。这些结果提供了对群体变异性起源的见解，并提出了常用实验方法中变异性产生的机制。
The dynamics and diversity of proliferating cellular populations are governed by the interplay between the growth and death rates among the various phenotypes within a colony. In addition, epigenetic multistability can cause cells to spontaneously switch from one phenotype to another. By examining a generalized form of the relative variance of populations and classifying it into intracolony and cross-colony contributions, we study the origins and consequences of cellular population variability. We find that the variability can depend highly on the initial conditions and the constraints placed on the population by the growth environment. We construct a two-phenotype model system and examine, analytically and numerically, its time-dependent variability in both unbounded and population-limited growth environments. We find that in unbounded growth environments the overall variability is strictly governed by the initial conditions. In contrast, when the overall population is limited by the environment, the system eventually relaxes to a unique fixed point regardless of the initial conditions. However, the transient decay to the fixed point depends highly on initial conditions, and the time scale over which the variability decays can be very long, depending on the intrinsic time scales of the system. These results provide insights into the origins of population variability and suggest mechanisms in which variability can arise in commonly used experimental approaches.