New Science research describes MultiFate, a genetic circuit design that unlocks controllable and scalable multistability in mammalian cells. The results provide a foundation for engineering multicellular behaviors in these cells.
An important goal for synthetic biology is to establish control systems that allow the direction of cells into multiple stable states, much like biological signaling systems do during organismal development. Zhu. devised a system that allows such control through designed zinc finger transcription factors that interact with one another through homo- and heterodimerization and can be regulated by small molecules that control dimerization and stability of the transcription factors .
To test the expandability of the MultiFate design, we integrated a third transcription factor into a MultiFate-2 cell line. As predicted by the model, the resulting MultiFate-3 cells could stably exist in seven distinct states for more than 18 days. Progressively reducing protein stability repeatedly bifurcated the system from septastability through hexastability to tristability, further recapitulating the progressive loss of cell fate potential in natural cell differentiation systems.
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