A data-driven computational model enables integrative and mechanistic characterization of dynamic macrophage polarization.
A data-driven computational model enables integrative and mechanistic characterization of dynamic macrophage polarization.
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数据驱动的计算模型使动态巨噬细胞极化的综合和机械表征成为可能。
DOI：
10.1016/j.isci.2021.102112
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Popel AS
中科院分区：
文献类型：
--
作者：
Zhao C;Medeiros TX;Sové RJ;Annex BH;Popel AS
巨噬细胞是高度可塑性的免疫细胞，它们动态地整合微环境信号以塑造自己的功能表型，这一过程被称为极化。在这里，我们开发了一个大规模的机械计算模型，首次实现了系统级的表征，从定量，时间，剂量依赖性和单细胞的角度来看，由复杂的多途径信号网络驱动的巨噬细胞极化。该模型进行了广泛的校准和验证，对文献，并集中在内部的实验数据。使用该模型，我们生成了动态表型图，以响应极化信号的多种组合;我们还探讨了基于模型的巨噬细胞的计算机模拟群体，以检查极化连续体在单细胞水平上的影响。此外，我们在外周动脉疾病的体外条件下分析了模型，以评估可能诱导治疗性巨噬细胞复极的策略。我们的模型是未来开发以网络为中心的综合“虚拟巨噬细胞”模拟平台的关键一步。巨噬细胞极化的大规模机械计算模型模型可进行定量、时间、剂量依赖性和单细胞模拟通过广泛的模型校准实现前所未有的预测分辨率模型分析为治疗性巨噬细胞复极化细胞生物学、系统生物学和计算机生物学提供了新的方向
Macrophages are highly plastic immune cells that dynamically integrate microenvironmental signals to shape their own functional phenotypes, a process known as polarization. Here we develop a large-scale mechanistic computational model that for the first time enables a systems-level characterization, from quantitative, temporal, dose-dependent, and single-cell perspectives, of macrophage polarization driven by a complex multi-pathway signaling network. The model was extensively calibrated and validated against literature and focused on in-house experimental data. Using the model, we generated dynamic phenotype maps in response to numerous combinations of polarizing signals; we also probed into an in silico population of model-based macrophages to examine the impact of polarization continuum at the single-cell level. Additionally, we analyzed the model under an in vitro condition of peripheral arterial disease to evaluate strategies that can potentially induce therapeutic macrophage repolarization. Our model is a key step toward the future development of a network-centric, comprehensive “virtual macrophage” simulation platform. A large-scale, mechanistic computational model of macrophage polarization Model enables quantitative, temporal, dose-dependent, and single-cell simulations Unprecedented predictive resolution empowered by extensive model calibration Model analyses provide new directions for therapeutic macrophage repolarization cell biology; systems biology; in silico biology
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通讯作者：
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