Stochastic Switching of Cell Fate in Microbes.
Microbes transiently differentiate into distinct, specialized cell types to generate functional diversity and cope with changing environmental conditions. Though alternate programs often entail radically different physiological and morphological states, recent single-cell studies have revealed that these crucial decisions are often left to chance. In these cases, the underlying genetic circuits leverage the intrinsic stochasticity of intracellular chemistry to drive transition between states. Understanding how these circuits transform transient gene expression fluctuations into lasting phenotypic programs will require a combination of quantitative modeling and extensive, time-resolved observation of switching events in single cells. In this article, we survey microbial cell fate decisions demonstrated to involve a random element, describe theoretical frameworks for understanding stochastic switching between states, and highlight recent advances in microfluidics that will enable characterization of key dynamic features of these circuits.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115; email: thomas.norman@ucsf.edu , ndlord@fas.harvard.edu , johan_paulsson@hms.harvard.edu.
Thomas M
TM
Norman
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115; email: thomas.norman@ucsf.edu , ndlord@fas.harvard.edu , johan_paulsson@hms.harvard.edu.
Nathan D
ND
Lord
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115; email: thomas.norman@ucsf.edu , ndlord@fas.harvard.edu , johan_paulsson@hms.harvard.edu.
Johan
J
Paulsson
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; email: losick@mcb.harvard.edu.
Richard
R
Losick
D001419:Bacteria / Q000737:chemistry / Q000145:classification / Q000166:cytology* / Q000235:genetics; D018407:Bacterial Physiological Phenomena; D059010:Single-Cell Analysis
bistability; development; gene expression noise; memory; microfluidics