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Synthetic multistability in mammalian cells

Zhu, Ronghui and del Rio-Salgado, Jesus M. and Garcia-Ojalvo, Jordi and Elowitz, Michael B. (2021) Synthetic multistability in mammalian cells. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210212-105104460

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Abstract

In multicellular organisms, gene regulatory circuits generate thousands of molecularly distinct, mitotically heritable states, through the property of multistability. Designing synthetic multistable circuits would provide insight into natural cell fate control circuit architectures and allow engineering of multicellular programs that require interactions among cells in distinct states. Here we introduce MultiFate, a naturally-inspired, synthetic circuit that supports long-term, controllable, and expandable multistability in mammalian cells. MultiFate uses engineered zinc finger transcription factors that transcriptionally self-activate as homodimers and mutually inhibit one another through heterodimerization. Using model-based design, we engineered MultiFate circuits that generate up to seven states, each stable for at least 18 days. MultiFate permits controlled state-switching and modulation of state stability through external inputs, and can be easily expanded with additional transcription factors. Together, these results provide a foundation for engineering multicellular behaviors in mammalian cells.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.02.10.430659DOIDiscussion Paper
https://data.caltech.edu/records/1882DOIData
ORCID:
AuthorORCID
Zhu, Ronghui0000-0001-8171-482X
Garcia-Ojalvo, Jordi0000-0002-3716-7520
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. This version posted February 11, 2021.
Record Number:CaltechAUTHORS:20210212-105104460
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210212-105104460
Official Citation:Synthetic multistability in mammalian cells. Ronghui Zhu, Jesus Maria del Rio-Salgado, Jordi Garcia-Ojalvo, Michael Elowitz. bioRxiv 2021.02.10.430659; doi: https://doi.org/10.1101/2021.02.10.430659
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108036
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Feb 2021 19:04
Last Modified:12 Feb 2021 19:04

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