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

• Published in: Nature communications Vol. 9; no. 1; pp. 2787 - 9
• Main Authors: Fang, Xiaona, Liu, Qiong, Bohrer, Christopher, Hensel, Zach, Han, Wei, Wang, Jin, Xiao, Jie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14/35; 38/1; 38/32; 38/77; 631/114/2114; 631/337/2265; 631/553/2691; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriophage lambda - genetics; Bacteriophage lambda - metabolism; Cell fate; Circuits; Decision making; Escherichia coli K12 - genetics; Escherichia coli K12 - metabolism; Escherichia coli K12 - virology; Gene expression; Gene Regulatory Networks; Genes, Reporter; Genes, Switch; Humanities and Social Sciences; Kinetics; Localization; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular chains; multidisciplinary; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Red Fluorescent Protein; Repressor Proteins - genetics; Repressor Proteins - metabolism; Science; Science (multidisciplinary); Switches; Switching theory; Transcription factors; Viral Regulatory and Accessory Proteins - genetics; Viral Regulatory and Accessory Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05071-1

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. Bistable switches are a common regulatory motif in cell fate decision-making circuits with two mutually exclusive expression states. Here the authors develop a bistable reporter system and report two additional expression states.