Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed-Accuracy Trade-off.

Area of Science:

• Cellular biology
• Systems biology
• Biophysics

Background:

• Precise ratio control of heterogeneous phenotypes in isogenic populations is vital for cell development and differentiation.
• Mechanisms underlying this ratio control, particularly concerning signal induction and gene expression stochasticity, remain poorly understood.

Purpose of the Study:

• To investigate the combined effects of signal induction and gene expression stochasticity on phenotypic multimodality.
• To identify and characterize strategies for controlling phenotypic ratios from homogeneous cell populations.

Main Methods:

• Utilized a combination of experimental and mathematical techniques.
• Analyzed the impact of signal induction within and outside bistable regions.
• Investigated the role of gene expression noise in different cellular contexts (high-noise bacteria vs. low-noise eukaryotes).

Main Results:

• Identified two distinct strategies for phenotypic ratio control, applicable to high-noise and low-noise environments.
• Demonstrated that noise-induced bimodality via induction within the bistable region is effective in noisy systems (e.g., bacteria).
• Showed that in low-noise systems (e.g., eukaryotes), controlled induction pulses outside the bistable region are necessary for bimodality.

Conclusions:

• Both identified strategies enable precise fractional differentiation.
• Noise levels, response time, and ratio tuning accuracy present trade-offs influencing strategy selection.
• The findings provide guidance for choosing appropriate ratio control strategies based on system-specific characteristics.