Cell size sensing in animal cells coordinates anabolic growth rates with cell cycle progression to maintain uniformity of cell size

The uniformity of cell size in healthy tissues suggests that control mechanisms might coordinate cell growth and division. We derived a method to assay whether cellular growth rates depend on cell size, by combining time-lapse microscopy and immunofluorescence to monitor how variance in cell size changes as cells grow. This analysis revealed two periods in the cell cycle when cell size variance decreases in a manner incompatible with unregulated growth, suggesting that cells sense their own size and adjust their growth rate to correct aberrations. Monitoring nuclear growth in live cells confirmed that these decreases in variance reflect a process that selectively inhibits growth of large cells while accelerating growth of small cells. We also detected cell-size-dependent adjustments of G1 length, which further reduce variability. Combining our assays with chemical/genetic perturbations confirmed that cells employ two strategies, adjusting both cell cycle length and growth rate, to maintain the appropriate size.