Regulated cell-to-cell variation in a cell-fate decision system

Area of Science:

• Cell Biology
• Systems Biology
• Genetics

Background:

• Eukaryotic cell-fate decisions involve complex signaling pathways.
• Understanding cell-to-cell variability is crucial for deciphering biological robustness and diversity.
• The yeast mating pheromone response pathway serves as a model system for studying cell-fate decisions.

Purpose of the Study:

• To quantitatively analyze cell-to-cell variability in the yeast mating pheromone response pathway.
• To identify and measure the sources of variation in this eukaryotic cell-fate decision system.
• To investigate the regulatory mechanisms underlying pathway and expression capacities.

Main Methods:

• Analysis of thousands of individual, genetically identical yeast cells.
• Quantitative measurement of cell-to-cell variation in signaling pathway output.
• Dissection of contributions from gene expression noise, pathway capacity, and expression capacity.

Main Results:

• Cell-to-cell variation is primarily driven by differences in pathway capacity and expression capacity, not expression noise.
• High expression capacity correlates with faster protein production and increased cell volume.
• MAP kinases Fus3 and Kss1 differentially regulate pathway capacity variation based on pheromone levels.
• Pathway capacity and expression capacity are negatively correlated, indicating a compensatory mechanism.

Conclusions:

• Cellular response precision is influenced by both signal transmission and protein synthesis capabilities.
• Specific MAP kinases play key roles in modulating cell-specific responses within a population.
• A compensatory mechanism exists between pathway and expression capacities to enhance pheromone response accuracy.