Regulated Cell to Cell Variation in a Cell Fate Decision System

ALEJANDRO COLMAN LERNER; ANDREW GORDON; EDUARD SERRA; TINA CHIN; ORNA RESNEKOV; DREW ENDY; GUSTAVO PESCE; ROGER BRENT

Boston, Massachusetts, Estados Unidos

Congreso; The Sixth International Conference on Systems Biology; 2005

CSBi (MIT), Bauer Center (Harvard), Broad Institute, Appl Biodynamics (Boston University) y Systems Biology (Harvard Medical School)

Here we studied the quantitative behavior and cell-to-cell variability of a prototypical eukaryotic cell-fate decision system, the mating pheromone response pathway in yeast. We dissected and measured sources of variation in system output, analyzing thousands of individual, genetically identical cells. For this analysis, we used different combinations of pheromone inducible and constitutive promoters driving the expression of YFP and CFP. Only a small proportion of total cell-to-cell variation is caused by random fluctuations in gene transcription and translation during the response (‘expression noise’). Instead, variation is dominated by differences in the capacity of individual cells to transmit signals through the pathway (‘pathway capacity’) and to express genes into proteins (‘expression capacity’). Cells with high expression capacity express proteins at a higher rate and increase in volume more rapidly. Our results also identify two mechanisms that regulate cell-to-cell variation in pathway capacity. First, the MAP kinase Fus3 suppresses variation at high pheromone levels, while the MAP kinase Kss1 enhances variation at low pheromone levels. Second, pathway capacity and expression capacity are negatively correlated, suggesting a compensatory mechanism that allows cells to respond more precisely to pheromone in the presence of a large variation in expression capacity.