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Synthetic mammalian signaling circuits for robust cell population control.


ABSTRACT: In multicellular organisms, cells actively sense and control their own population density. Synthetic mammalian quorum-sensing circuits could provide insight into principles of population control and extend cell therapies. However, a key challenge is reducing 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. We designed a paradoxical population control circuit, termed "Paradaux," in which auxin stimulates and inhibits net cell growth at different concentrations. This circuit limited population size over extended timescales of up to 42 days of continuous culture. By contrast, when operating in a non-paradoxical regime, population control became more susceptible to mutational escape. These results establish auxin as a versatile "private" communication system and demonstrate that paradoxical circuit architectures can provide robust population control.

SUBMITTER: Ma Y 

PROVIDER: S-EPMC8995209 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Synthetic mammalian signaling circuits for robust cell population control.

Ma Yitong Y   Budde Mark W MW   Mayalu Michaëlle N MN   Zhu Junqin J   Lu Andrew C AC   Murray Richard M RM   Elowitz Michael B MB  

Cell 20220301 6


In multicellular organisms, cells actively sense and control their own population density. Synthetic mammalian quorum-sensing circuits could provide insight into principles of population control and extend cell therapies. However, a key challenge is reducing 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. We designed a paradoxical population control circuit  ...[more]

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