Synthetic mammalian signaling circuits for robust cell population control
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|Synthetic mammalian signaling circuits for robust cell population control
|Yitong Ma, Mark W. Budde, Michaëlle N. Mayalu, Junqin Zhu, Richard M. Murray and Michael B. Elowitz
|Submitted, Cell Systems
|In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. Further, we show that a “paradoxical” circuit design, in which auxin stimulates and inhibits net cell growth at different concentrations, achieves population control that is robust to cheater mutations, controlling growth for 43 days of continuous culture. By contrast, a non-paradoxical control circuit limited growth but was susceptible to mutations. These results establish a foundation for future cell therapies that can respond to and control their own population sizes.