Emergent Stem Cell Homeostasis in the C. elegans Germline Is Revealed by Hybrid Modeling
Emergent Stem Cell Homeostasis in the C. elegans Germline Is Revealed by Hybrid Modeling
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DOI：
10.1016/j.bpj.2015.06.007
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发表时间：
2015-07-21
影响因子：
3.4
通讯作者：
Fisher, Jasmin
中科院分区：
文献类型：
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作者：
Hall, Benjamin A.;Piterman, Nir;Fisher, Jasmin
细胞生长、分化和凋亡之间的稳态的建立对于器官发生是至关重要的。干细胞通过从有丝分裂增殖到不对称细胞分裂和分化来响应时间和空间调节信号。信号通路的可执行计算机模型可以通过将详细的化学动力学简化为离散的有限形式来准确地再现广泛的生物现象。此外，协调的细胞运动和物理细胞间的相互作用是形成三维结构所必需的，三维结构是器官的构建块。为了捕捉所有这些方面，我们已经开发了一个混合的可执行/物理模型描述干细胞增殖，分化和稳态秀丽隐杆线虫种系。使用这种混合模型，我们能够跟踪生殖细胞分化过程中的细胞谱系和动态细胞运动。我们进一步展示了细胞凋亡如何调节生殖腺中生殖细胞的稳态，并提出了细胞间压力在发育控制中的作用。最后，我们使用该模型来演示如何从混合系统中开发可执行模型，确定一种机制，确保在存在不稳定的命运模式的不变性。
The establishment of homeostasis among cell growth, differentiation, and apoptosis is of key importance for organogenesis. Stem cells respond to temporally and spatially regulated signals by switching from mitotic proliferation to asymmetric cell division and differentiation. Executable computer models of signaling pathways can accurately reproduce a wide range of biological phenomena by reducing detailed chemical kinetics to a discrete, finite form. Moreover, coordinated cell movements and physical cell-cell interactions are required for the formation of three-dimensional structures that are the building blocks of organs. To capture all these aspects, we have developed a hybrid executable/physical model describing stem cell proliferation, differentiation, and homeostasis in the Caenorhabditis elegans germline. Using this hybrid model, we are able to track cell lineages and dynamic cell movements during germ cell differentiation. We further show how apoptosis regulates germ cell homeostasis in the gonad, and propose a role for intercellular pressure in developmental control. Finally, we use the model to demonstrate how an executable model can be developed from the hybrid system, identifying a mechanism that ensures invariance in fate patterns in the presence of instability.