Cell size homeostasis is tightly controlled throughout the cell cycle

Cell size homeostasis is tightly controlled throughout the cell cycle

January 5, 2024 | Xili Liu, Jiawei Yan, Marc W. Kirschner
Cell size homeostasis is tightly controlled throughout the cell cycle. Proliferating cells maintain a stable size distribution despite stochastic noise in growth rate, cell cycle phase duration, and cell division asymmetry. The widely accepted model suggests that cell size is regulated at the G1/S transition, with cells pausing until they reach a critical size. However, this model cannot fully explain how cells with impaired G1/S control maintain stable size distributions or how cell size variation occurs during later phases. Using computationally enhanced quantitative phase microscopy (ceQPM), researchers measured cell dry mass in cultured human cell lines and found that cell mass homeostasis is maintained throughout the cell cycle, not just at G1/S. The coefficient of variation (CV) of cell mass begins to decline before G1/S and continues to decrease during S and G2 phases. Cell mass homeostasis is achieved through mass-dependent cell cycle regulation and growth rate modulation. These processes work together to reduce cell mass variation. The study challenges the traditional G1/S checkpoint model and suggests that cell size control involves regulation of multiple phases of the cell cycle. The findings reveal previously unappreciated principles of cell size control in proliferating cells and suggest that similar regulatory processes may operate in terminally differentiated cells. The study highlights the importance of understanding the molecular mechanisms underlying cell size control.Cell size homeostasis is tightly controlled throughout the cell cycle. Proliferating cells maintain a stable size distribution despite stochastic noise in growth rate, cell cycle phase duration, and cell division asymmetry. The widely accepted model suggests that cell size is regulated at the G1/S transition, with cells pausing until they reach a critical size. However, this model cannot fully explain how cells with impaired G1/S control maintain stable size distributions or how cell size variation occurs during later phases. Using computationally enhanced quantitative phase microscopy (ceQPM), researchers measured cell dry mass in cultured human cell lines and found that cell mass homeostasis is maintained throughout the cell cycle, not just at G1/S. The coefficient of variation (CV) of cell mass begins to decline before G1/S and continues to decrease during S and G2 phases. Cell mass homeostasis is achieved through mass-dependent cell cycle regulation and growth rate modulation. These processes work together to reduce cell mass variation. The study challenges the traditional G1/S checkpoint model and suggests that cell size control involves regulation of multiple phases of the cell cycle. The findings reveal previously unappreciated principles of cell size control in proliferating cells and suggest that similar regulatory processes may operate in terminally differentiated cells. The study highlights the importance of understanding the molecular mechanisms underlying cell size control.
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