TY - JOUR
T1 - Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch
AU - Fang, Xiaona
AU - Liu, Qiong
AU - Bohrer, Christopher
AU - Hensel, Zach
AU - Han, Wei
AU - Wang, Jin
AU - Xiao, Jie
N1 - Funding Information:
We thank Dr. Thomas E. Kuhlman for the gifts of pTKRED, pTKIP, pTKS/CS; Dr. Roland Baker for the gift of pCG001; Dr. Joe Pogliano for the gift of pZZ6. This work was supported by NSF CAREER Award (0746796), March of Dimes Research grant (1-FY2011), NSF EAGER MCB1019000, NSF PHYS 76066, NSFC 91430217, and LISBOA-01-0145-FEDER-007660.
Funding Information:
This work was supported by NSF CAREER Award (0746796), March of Dimes Research grant (1- FY2011), NSF EAGER MCB1019000, NSF PHYS 76066, NSFC 91430217, and LISBOA-01-0145-FEDER-007660.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85050388148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050388148&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05071-1
DO - 10.1038/s41467-018-05071-1
M3 - Article
C2 - 30018349
AN - SCOPUS:85050388148
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2787
ER -