Circuit Design Features of a Stable Two-Cell System.,Cell

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Circuit Design Features of a Stable Two-Cell System.
Cell ( IF 45.5 ) Pub Date : 2018-Feb-08 , DOI: 10.1016/j.cell.2018.01.015
Xu Zhou ₁ , Ruth A Franklin ₁ , Miri Adler ₂ , Jeremy B Jacox ₃ , Will Bailis ₁ , Justin A Shyer ₁ , Richard A Flavell ₁ , Avi Mayo ₂ , Uri Alon ₂ , Ruslan Medzhitov ₁

Affiliation

Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit with specific properties that ensure homeostasis. Here, we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. Analytical screening of all possible two-cell circuit topologies revealed the circuit features sufficient for stability, including environmental constraint and negative-feedback regulation. Moreover, we found that cell-cell contact is essential for the stability of the macrophage-fibroblast circuit. These findings illustrate principles of cell circuit design and provide a quantitative perspective on cell interactions.

中文翻译：

稳定的两电池系统的电路设计特征。

组织内的细胞通讯由多种旁分泌信号介导，包括控制细胞存活和增殖的生长因子。细胞及其产生和接收的生长因子构成了具有确保体内平衡的特定特性的回路。在这里，我们使用计算和实验方法来表征基于巨噬细胞和成纤维细胞（大多数哺乳动物组织中发现的两种细胞类型）之间生长因子交换的细胞回路的特征。我们发现巨噬细胞-成纤维细胞回路是稳定的并且对扰动具有鲁棒性。对所有可能的两电池电路拓扑的分析筛选揭示了电路具有足够的稳定性的特性，包括环境约束和负反馈调节。此外，我们发现细胞与细胞的接触对于巨噬细胞-成纤维细胞回路的稳定性至关重要。这些发现阐明了细胞电路设计的原理，并提供了细胞相互作用的定量视角。

更新日期：2018-02-01

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