Novel generic models for differentiating stem cells reveal oscillatory mechanisms.
Novel generic models for differentiating stem cells reveal oscillatory mechanisms.
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DOI：
10.1098/rsif.2021.0442
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
Rocco A
中科院分区：
文献类型：
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作者：
Farjami S;Camargo Sosa K;Dawes JHP;Kelsh RN;Rocco A
理解细胞命运选择仍然是发育生物学的核心挑战。我们提出了一类简单但生物激励的细胞分化数学模型，这些模型一般会产生振荡，因此建议替代基于沃丁顿表观遗传格局的标准框架。这些模型允许我们提出两种描述分化过程的一般动态情景。在第一种情况下，单个控制参数的逐渐变化是进入和退出振荡区域的原因。在第二种情况下，两个控制参数不同：一个负责进入，另一个负责退出振荡区域。我们分析了标准阻滞剂和它的四个变种，并展示了与每种情景相关的动力学行为。我们对相关的分叉进行了彻底的分析，并认为具有这些抑制物类似特征的基因调控网络是描述通过振荡过程进行细胞命运选择的有前途的候选者。
Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.