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Synthetic mammalian signaling circuits for robust cell population control

Ma, Yitong and Budde, Mark W. and Mayalu, Michaëlle N. and Zhu, Junqin and Murray, Richard M. and Elowitz, Michael B. (2020) Synthetic mammalian signaling circuits for robust cell population control. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200909-145940519

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Abstract

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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.09.02.278564DOIDiscussion Paper
https://doi.org/10.22002/D1.1613DOIData
https://www.addgene.org/plasmids/articles/28212030Related ItemCode
https://github.com/labowitz/auxin_paradox_matlab_codeRelated ItemCode
ORCID:
AuthorORCID
Ma, Yitong0000-0003-4446-7326
Budde, Mark W.0000-0002-4359-1424
Mayalu, Michaëlle N.0000-0002-9678-0157
Zhu, Junqin0000-0002-8159-6402
Murray, Richard M.0000-0002-5785-7481
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Posted September 03, 2020. Data and material availability: The plasmid GenBank files, raw data, and processing/plotting scripts for generating the figures shown in this paper are available at data.caltech.edu (http://dx.doi.org/10.22002/D1.1613). Key constructs will be made available through addgene.com (https://www.addgene.org/plasmids/articles/28212030/) and key cell lines will be available upon request. The code for the mathematical modeling section (Figure 5 and S4) is available at github.com: (https://github.com/labowitz/auxin_paradox_matlab_code).
Record Number:CaltechAUTHORS:20200909-145940519
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200909-145940519
Official Citation:Synthetic mammalian signaling circuits for robust cell population control. Yitong Ma, Mark W. Budde, Michaëlle N. Mayalu, Junqin Zhu, Richard M. Murray, Michael B. Elowitz. bioRxiv 2020.09.02.278564; doi: https://doi.org/10.1101/2020.09.02.278564
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105302
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Sep 2020 23:17
Last Modified:09 Sep 2020 23:17

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