Toscano-Ochoa Carlos, Garcia-Ojalvo Jordi
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, Spain.
iScience. 2021 Mar 25;24(4):102347. doi: 10.1016/j.isci.2021.102347. eCollection 2021 Apr 23.
Processing time-dependent information requires cells to quantify the duration of past regulatory events and program the time span of future signals. At the single-cell level, timer mechanisms can be implemented with genetic circuits. However, such systems are difficult to implement in single cells due to saturation in molecular components and stochasticity in the limited intracellular space. In contrast, multicellular implementations outsource some of the components of information-processing circuits to the extracellular space, potentially escaping these constraints. Here, we develop a theoretical framework, based on trilinear coordinate representation, to study the collective behavior of populations composed of three cell types under stationary conditions. This framework reveals that distributing different processes (in our case the production, detection and degradation of a time-encoding signal) across distinct strains enables the implementation of a multicellular timer. Our analysis also shows that the circuit can be easily tunable by varying the cellular composition of the consortium.
处理随时间变化的信息需要细胞量化过去调控事件的持续时间，并规划未来信号的时间跨度。在单细胞水平上，定时器机制可以通过基因回路来实现。然而，由于分子成分的饱和以及有限细胞内空间中的随机性，此类系统在单细胞中难以实现。相比之下，多细胞实现方式将信息处理回路的一些组件外包到细胞外空间，有可能摆脱这些限制。在这里，我们基于三线坐标表示法开发了一个理论框架，以研究在稳定条件下由三种细胞类型组成的群体的集体行为。该框架表明，将不同的过程（在我们的案例中是时间编码信号的产生、检测和降解）分布在不同的菌株中能够实现多细胞定时器。我们的分析还表明，通过改变群落的细胞组成，该回路可以很容易地进行调节。
