The study investigates the mechanisms underlying cell size homeostasis during the cell cycle. Using computationally enhanced quantitative phase microscopy (ceQPM), the researchers measured the dry mass of individual cells in cultured human cell lines throughout the cell cycle. They found that cell mass homeostasis is maintained despite disruptions to the G1/S transition and variations in cell growth rates. The coefficient of variation (CV) in cell mass decreases before the G1/S transition and continues to decline throughout the S and G2 phases. The study challenges the traditional model that attributes size control solely to the G1/S checkpoint, showing that mass homeostasis is regulated throughout the cell cycle. Additionally, the researchers found that both mass-dependent cell cycle regulation and mass-dependent growth rate modulation contribute to reducing cell mass variation. They also observed that the duration of cell cycle phases, such as G1, S, and G2, is negatively correlated with cell mass, indicating that feedback mechanisms exist outside of the G1 phase. The findings suggest that accurate cell mass homeostasis is achieved through the interplay and coordination of these processes, providing new insights into the underlying molecular mechanisms of cell size control.The study investigates the mechanisms underlying cell size homeostasis during the cell cycle. Using computationally enhanced quantitative phase microscopy (ceQPM), the researchers measured the dry mass of individual cells in cultured human cell lines throughout the cell cycle. They found that cell mass homeostasis is maintained despite disruptions to the G1/S transition and variations in cell growth rates. The coefficient of variation (CV) in cell mass decreases before the G1/S transition and continues to decline throughout the S and G2 phases. The study challenges the traditional model that attributes size control solely to the G1/S checkpoint, showing that mass homeostasis is regulated throughout the cell cycle. Additionally, the researchers found that both mass-dependent cell cycle regulation and mass-dependent growth rate modulation contribute to reducing cell mass variation. They also observed that the duration of cell cycle phases, such as G1, S, and G2, is negatively correlated with cell mass, indicating that feedback mechanisms exist outside of the G1 phase. The findings suggest that accurate cell mass homeostasis is achieved through the interplay and coordination of these processes, providing new insights into the underlying molecular mechanisms of cell size control.