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

Xiaona Fang, Qiong Liu, Christopher Bohrer, Zach Hensel, Wei Han, Jin Wang () and Jie Xiao ()
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Xiaona Fang: Changchun Institute of Applied Chemistry
Qiong Liu: Changchun Institute of Applied Chemistry
Christopher Bohrer: Johns Hopkins School of Medicine
Zach Hensel: Johns Hopkins School of Medicine
Wei Han: Jilin University
Jin Wang: Changchun Institute of Applied Chemistry
Jie Xiao: Johns Hopkins School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05071-1

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