Format

Send to

Choose Destination
Nat Commun. 2018 Jul 17;9(1):2787. doi: 10.1038/s41467-018-05071-1.

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

Fang X1,2,3,4, Liu Q1, Bohrer C2, Hensel Z2,5, Han W3, Wang J6,7,8, Xiao J9.

Author information

1
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Changchun, 130022, China.
2
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
3
College of Physics, Jilin University, Changchun, 130012, China.
4
Department of Chemistry and Physics, Stony Brook University, Stony Brook, NY, 11790, USA.
5
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.
6
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Changchun, 130022, China. jin.wang.1@stonybrook.edu.
7
College of Physics, Jilin University, Changchun, 130012, China. jin.wang.1@stonybrook.edu.
8
Department of Chemistry and Physics, Stony Brook University, Stony Brook, NY, 11790, USA. jin.wang.1@stonybrook.edu.
9
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. xiao@jhmi.edu.

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.

PMID:
30018349
PMCID:
PMC6050291
DOI:
10.1038/s41467-018-05071-1
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center