Modelling hair follicle growth dynamics as an excitable medium.
Modelling hair follicle growth dynamics as an excitable medium.
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DOI：
10.1371/journal.pcbi.1002804
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发表时间：
2012
影响因子：
4.3
通讯作者：
Baker RE
中科院分区：
文献类型：
--
作者：
Murray PJ;Maini PK;Plikus MV;Chuong CM;Baker RE
毛囊系统是研究再生成人上皮组织中干细胞行为的一个易处理的模型。然而，尽管有许多空间尺度的观察（分子，细胞，卵泡和多卵泡），目前还不清楚是什么机制支持卵泡生长周期。在这项研究中，我们试图解决这个问题，通过描述如何生长动态的一大人口的卵泡可以被视为一个经典的兴奋介质。在分子尺度上定义漫画的相互作用，并将单个卵泡作为一个功能单位，提出了一个最小模型，其中卵泡生长周期是一个新兴的现象。表达式推导，在参数表示分子调控，在周期的不同功能阶段所花费的时间，一种形式主义，允许该模型直接与以前的元胞自动机模型和实验测量在单卵泡规模进行比较。一个多卵泡模型的构建和数值模拟被用来证明良好的定性协议与一系列的实验观察。值得注意的是，可兴奋介质方程表现出更广泛的家庭的解决方案比以前的工作，我们演示了如何改变分子调控的参数变化可以解释扰动模式Wnt过度表达和BMP下调小鼠模型。进一步的实验方案，可以用来测试模型的基本前提的建议。从我们的工作中得出的关键结论是，激活剂和抑制剂之间的正向和负向调节相互作用可以在毛囊和多毛囊空间尺度上引起一系列实验观察到的现象，因此，可以代表毛囊生长的核心机制。虽然调控卵泡生长周期的分子相互作用已经开始被发现，但调控周期性的基本相互作用仍然难以捉摸。在这项研究中，我们开发了一个模型，其中我们忽略生物物理效应（因此形态学变化）治疗每个卵泡作为一个功能单位。然后，我们描述了漫画的相互作用，在卵泡规模的属性，耦合卵泡的字段可以被视为一个可兴奋的介质。我们进行了一系列的模拟，证明定性协议与实验观察。此外，建模结果表明，可能代表头发生长调节的关键基本原则的调节机制。
The hair follicle system represents a tractable model for the study of stem cell behaviour in regenerative adult epithelial tissue. However, although there are numerous spatial scales of observation (molecular, cellular, follicle and multi follicle), it is not yet clear what mechanisms underpin the follicle growth cycle. In this study we seek to address this problem by describing how the growth dynamics of a large population of follicles can be treated as a classical excitable medium. Defining caricature interactions at the molecular scale and treating a single follicle as a functional unit, a minimal model is proposed in which the follicle growth cycle is an emergent phenomenon. Expressions are derived, in terms of parameters representing molecular regulation, for the time spent in the different functional phases of the cycle, a formalism that allows the model to be directly compared with a previous cellular automaton model and experimental measurements made at the single follicle scale. A multi follicle model is constructed and numerical simulations are used to demonstrate excellent qualitative agreement with a range of experimental observations. Notably, the excitable medium equations exhibit a wider family of solutions than the previous work and we demonstrate how parameter changes representing altered molecular regulation can explain perturbed patterns in Wnt over-expression and BMP down-regulation mouse models. Further experimental scenarios that could be used to test the fundamental premise of the model are suggested. The key conclusion from our work is that positive and negative regulatory interactions between activators and inhibitors can give rise to a range of experimentally observed phenomena at the follicle and multi follicle spatial scales and, as such, could represent a core mechanism underlying hair follicle growth. Although the molecular interactions that regulate the follicle growth cycle have begun to be uncovered, the fundamental interactions that regulate periodicity remain elusive. In this study we develop a model in which we neglect biophysical effects (and hence morphological changes) by treating each follicle as a functional unit. We then describe caricature interactions at the follicle scale which have the property that a field of coupled follicles can be treated as an excitable medium. We perform a range of simulations that demonstrate qualitative agreement with experimental observations. Furthermore, the modelling results suggest a regulatory mechanism that might represent a key underlying principle in the regulation of hair growth.
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影响因子：
4.5
作者：
Lin KK;Kumar V;Geyfman M;Chudova D;Ihler AT;Smyth P;Paus R;Takahashi JS;Andersen B
通讯作者：
Andersen B
影响因子：
1.7
作者：
MCKEAN, HP
通讯作者：
MCKEAN, HP
DOI：
10.1038/sj.jidsp.5640241
发表时间：
1999-12-01
影响因子：
--
作者：
Paus, R;Müller-Röver, S;Botchkarev, VA
通讯作者：
Botchkarev, VA
DOI：
10.1126/science.1201647
发表时间：
2011-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Plikus MV;Baker RE;Chen CC;Fare C;de la Cruz D;Andl T;Maini PK;Millar SE;Widelitz R;Chuong CM
通讯作者：
Chuong CM
影响因子：
6.5
作者：
Plikus, Maksim V.
通讯作者：
Plikus, Maksim V.