Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch

Nature Communications
Xiaona FangJie Xiao

Abstract

Bistable switches are common gene regulatory motifs directing two mutually exclusive cell fates. Theoretical studies suggest that bistable switches are sufficient to encode more than two cell fates without rewiring the circuitry due to the non-equilibrium, heterogeneous cellular environment. However, such a scenario has not been experimentally observed. Here by developing a new, dual single-molecule gene-expression reporting system, we find that for the two mutually repressing transcription factors CI and Cro in the classic bistable bacteriophage λ switch, there exist two new production states, in which neither CI nor Cro is produced, or both CI and Cro are produced. We construct the corresponding potential landscape and map the transition kinetics among the four production states. These findings uncover cell fate potentials beyond the classical picture of bistable switches, and open a new window to explore the genetic and environmental origins of the cell fate decision-making process in gene regulatory networks.

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Citations

Feb 20, 2019·PLoS Computational Biology·M Ali Al-RadhawiEduardo D Sontag
Sep 23, 2018·The Journal of Biological Chemistry·Qiuyan ShaoLanying Zeng
Oct 9, 2019·Nature Communications·M PájaroA A Alonso
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Nov 8, 2020·Nature Communications·Ferdinand GreissRoy Bar-Ziv
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May 7, 2021·Annual Review of Biophysics·Michael G CortesGábor Balázsi

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

MATLAB
DuTrAc

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