Noise-Driven Stem Cell and Progenitor Population Dynamics
Noise-Driven Stem Cell and Progenitor Population Dynamics
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DOI：
10.1371/journal.pone.0002922
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发表时间：
2008-08-13
期刊：
影响因子：
3.7
通讯作者：
Galle, Joerg
中科院分区：
文献类型：
--
作者：
Hoffmann, Martin;Chang, Hannah H.;Galle, Joerg
背景：干细胞状态的维持和终末分化之间的平衡受到细胞环境的影响。长期以来，这些态之间的转换一直被理解为分子网络吸引子状态之间的转换。在这里，随机波动要么被抑制，要么可以触发转变，但它们实际上并不决定吸引子的状态。方法/主要发现：我们提出了一个新的数学概念，其中干细胞和祖细胞群体动态被描述为一个由细胞增殖和分化状态的微小波动引起的概率过程。这些状态波动反映了潜在调控网络的不同激活模式之间的随机转换。重要的是，相关的噪声幅度是状态相关的，并由环境设置。它们的可变性决定了吸引子的状态，从而实际上控制了种群的动态。这个模型定量地再现了观察到的早幼粒细胞前体细胞分化和去分化的动力学。结论/意义：因此，外部信号的状态特异性噪声调制可以在控制干细胞和祖细胞群体动力学方面发挥作用。我们建议进行后续实验，以量化环境对细胞噪声调节的印记影响。
Background: The balance between maintenance of the stem cell state and terminal differentiation is influenced by the cellular environment. The switching between these states has long been understood as a transition between attractor states of a molecular network. Herein, stochastic fluctuations are either suppressed or can trigger the transition, but they do not actually determine the attractor states.Methodology/Principal Findings: We present a novel mathematical concept in which stem cell and progenitor population dynamics are described as a probabilistic process that arises from cell proliferation and small fluctuations in the state of differentiation. These state fluctuations reflect random transitions between different activation patterns of the underlying regulatory network. Importantly, the associated noise amplitudes are state-dependent and set by the environment. Their variability determines the attractor states, and thus actually governs population dynamics. This model quantitatively reproduces the observed dynamics of differentiation and dedifferentiation in promyelocytic precursor cells.Conclusions/Significance: Consequently, state-specific noise modulation by external signals can be instrumental in controlling stem cell and progenitor population dynamics. We propose follow-up experiments for quantifying the imprinting influence of the environment on cellular noise regulation.