Global dynamics of two-compartment models for cell production systems with regulatory mechanisms
Global dynamics of two-compartment models for cell production systems with regulatory mechanisms
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DOI：
10.1016/j.mbs.2013.07.006
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发表时间：
2013-10-01
影响因子：
4.3
通讯作者：
Vivanco, Maria dM.
中科院分区：
文献类型：
--
作者：
Getto, Philipp;Marciniak-Czochra, Anna;Vivanco, Maria dM.
我们提出了一个具有非线性调节反馈环的递阶细胞生产系统的两室模型的全局稳定性分析。该模型描述了细胞分化过程，其中干细胞分裂速率或自我更新分数由成熟细胞的数量调节。二室系统构成了Marciniak-Czochra及其合作者最近提出的多室模型的基本版本[25]，以研究造血系统的动力学。使用全局稳定性分析，我们比较不同的监管机制。对于这两个模型，我们证明了存在一个唯一的正平衡点是全局渐近稳定的当且仅当各自的再生数超过1。证明是基于构造李雅普诺夫函数，这是适当的处理特定的非线性模型。此外，我们提出了一个新的模型来测试生物学假说的分化细胞的比例的调节。我们发现，这种调节机制是无法维持稳态，并导致无限的细胞生长。潜在的生物影响进行了讨论。(C)2013 Elsevier Inc. All rights reserved.
We present a global stability analysis of two-compartment models of a hierarchical cell production system with a nonlinear regulatory feedback loop. The models describe cell differentiation processes with the stem cell division rate or the self-renewal fraction regulated by the number of mature cells. The two-compartment systems constitute a basic version of the multicompartment models proposed recently by Marciniak-Czochra and collaborators [25] to investigate the dynamics of the hematopoietic system. Using global stability analysis, we compare different regulatory mechanisms. For both models, we show that there exists a unique positive equilibrium that is globally asymptotically stable if and only if the respective reproduction numbers exceed one. The proof is based on constructing Lyapunov functions, which are appropriate to handle the specific nonlinearities of the model. Additionally, we propose a new model to test biological hypothesis on the regulation of the fraction of differentiating cells. We show that such regulatory mechanism is incapable of maintaining homeostasis and leads to unbounded cell growth. Potential biological implications are discussed. (C) 2013 Elsevier Inc. All rights reserved.