Feedback between stochastic gene networks and population dynamics enables cellular decision-making

Sci Adv. 2024 May 24;10(21):eadl4895. doi: 10.1126/sciadv.adl4895. Epub 2024 May 24.

Abstract

Phenotypic selection occurs when genetically identical cells are subject to different reproductive abilities due to cellular noise. Such noise arises from fluctuations in reactions synthesizing proteins and plays a crucial role in how cells make decisions and respond to stress or drugs. We propose a general stochastic agent-based model for growing populations capturing the feedback between gene expression and cell division dynamics. We devise a finite state projection approach to analyze gene expression and division distributions and infer selection from single-cell data in mother machines and lineage trees. We use the theory to quantify selection in multi-stable gene expression networks and elucidate that the trade-off between phenotypic switching and selection enables robust decision-making essential for synthetic circuits and developmental lineage decisions. Using live-cell data, we demonstrate that combining theory and inference provides quantitative insights into bet-hedging-like response to DNA damage and adaptation during antibiotic exposure in Escherichia coli.

MeSH terms

  • Cell Division / genetics
  • Escherichia coli* / genetics
  • Gene Regulatory Networks*
  • Stochastic Processes