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Winner-takes-all resource competition redirects cascading cell fate transitions

Author

Listed:
  • Rong Zhang

    (Arizona State University)

  • Hanah Goetz

    (Arizona State University)

  • Juan Melendez-Alvarez

    (Arizona State University)

  • Jiao Li

    (Arizona State University
    Zhejiang University)

  • Tian Ding

    (Zhejiang University)

  • Xiao Wang

    (Arizona State University)

  • Xiao-Jun Tian

    (Arizona State University)

Abstract

Failure of modularity remains a significant challenge for assembling synthetic gene circuits with tested modules as they often do not function as expected. Competition over shared limited gene expression resources is a crucial underlying reason. It was reported that resource competition makes two seemingly separate genes connect in a graded linear manner. Here we unveil nonlinear resource competition within synthetic gene circuits. We first build a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve two successive cell fate transitions. Interestingly, we find that the in vivo transition path was redirected as the activation of one switch always prevails against the other, contrary to the theoretically expected coactivation. This qualitatively different type of resource competition between the two modules follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the modules. To decouple the resource competition, we construct a two-strain circuit, which achieves successive activation and stable coactivation of the two switches. These results illustrate that a highly nonlinear hidden interaction between the circuit modules due to resource competition may cause counterintuitive consequences on circuit functions, which can be controlled with a division of labor strategy.

Suggested Citation

  • Rong Zhang & Hanah Goetz & Juan Melendez-Alvarez & Jiao Li & Tian Ding & Xiao Wang & Xiao-Jun Tian, 2021. "Winner-takes-all resource competition redirects cascading cell fate transitions," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21125-3
    DOI: 10.1038/s41467-021-21125-3
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    Cited by:

    1. Hyeon Jo & Youngsok Bang, 2023. "RETRACTED ARTICLE: Factors influencing continuance intention of participants in crowdsourcing," Palgrave Communications, Palgrave Macmillan, vol. 10(1), pages 1-13, December.
    2. Kirill Sechkar & Harrison Steel & Giansimone Perrino & Guy-Bart Stan, 2024. "A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Carlos Barajas & Hsin-Ho Huang & Jesse Gibson & Luis Sandoval & Domitilla Vecchio, 2022. "Feedforward growth rate control mitigates gene activation burden," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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