Cellular population dynamics control the robustness of the stem cell niche.
Cellular population dynamics control the robustness of the stem cell niche.
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DOI：
10.1242/bio.013714
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发表时间：
2015-10-09
期刊：
影响因子：
2.4
通讯作者：
Stumpf MP
中科院分区：
文献类型：
--
作者：
MacLean AL;Kirk PD;Stumpf MP
在细胞群中，命运决定是由细胞内在因素和细胞外在因素的不确定组合控制的。就干细胞而言，干细胞生态位被认为通过干细胞与一种或多种其他有助于形成生态位条件的细胞类型之间的通讯和相互作用来维持“干性”。为了研究干细胞层次结构中细胞命运决定的稳健性以及生态位所扮演的角色，我们引入了干细胞和祖细胞、它们的后代以及它们在生态位中相互作用的简单数学模型。这些模型捕捉了增殖和分化的基本过程，使我们能够考虑关于生态位介导的信号反馈如何调节生态位动态的替代可能性。这些干细胞生态位系统的广义稳定性分析使我们能够描述每个模型的稳定性特性。我们发现，尽管可行状态的数量取决于模型，但它们的稳定性概率通常并不依赖于模型：干细胞生态位模型在各种参数下都是稳定的。我们证明了生态位介导的反馈增加了稳定状态的数量，并展示了不同的细胞状态如何具有不同的分支特征。因此，干细胞生态位介导的生态反馈和相互作用为干细胞和祖细胞群体动态提供了（令人惊讶的）高水平的稳健性。此外，细胞与细胞之间的相互作用足以使干细胞及其后代群体实现稳定性并维持体内平衡。我们表明，生态位的稳健性——以及生态位中干细胞库的稳健性——仅微弱地（如果有的话）取决于生态位构成的复杂性：简单和复杂的生态位系统都能够支持强大和稳定的干细胞动力学。摘要：干细胞生态位动态对于外部和生理扰动非常强大，因为增殖和分化是通过依赖共享的生态位环境自然平衡和控制的。
Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics. Summary: Stem cell niche dynamics are very robust to external and physiological perturbations because proliferation and differentiation are naturally balanced and controlled by the reliance on a shared niche environment.