Nature Communications , 2018, 9 (1), 3275.

Size control in mammalian cells involves modulation of both growth rate and cell cycle duration

Cadart, Clotilde | Monnier, Sylvain | Grilli, Jacopo | Sáez, Pablo J. | Srivastava, Nishit | Attia, Rafaele | Terriac, Emmanuel | Baum, Buzz | Cosentino-Lagomarsino, Marco | Piel, Matthieu

Despite decades of research, how mammalian cell size is controlled remains unclear because of the difficulty of directly measuring growth at the single-cell level. Here we report direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells. We find that, in a majority of cell types, the volume added across the cell cycle shows little or no correlation to cell birth size, a homeostatic behavior called “adder”. This behavior involves modulation of G1 or S-G2 duration and modulation of growth rate. The precise combination of these mechanisms depends on the cell type and the growth condition. We have developed a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells. This reveals that a near-adder behavior is the most common type of size control and highlights the importance of growth rate modulation to size control in mammalian cells.

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