Biologists have long been concerned about what constrains variation in cell size, but progress in this field has been slow and stymied by experimental limitations1. Here we describe a new method, ergodic rate analysis (ERA), that uses single-cell measurements of fixed steady-state populations to accurately infer the rates of molecular events, including rates of cell growth. ERA exploits the fact that the number of cells in a particular state is related to the average transit time through that state2. With this method, it is possible to calculate full time trajectories of any feature that can be labelled in fixed cells, for example levels of phosphoproteins or total cellular mass. Using ERA we find evidence for a size-discriminatory process at the G1/S transition that acts to decrease cell-to-cell size variation.
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We thank A. Klein, Y. Merbl, S. Tal and J. Toettcher for consistent and valuable insights at the beginning of and throughout this project. We thank J. Waters and the staff of The Nikon Imaging Center at Harvard Medical School for help and support. We especially thank R. Ward for her critique of the paper and the National Institute of General Medical Sciences (GM26875) for support of this work.
The authors declare no competing financial interests.
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Kafri, R., Levy, J., Ginzberg, M. et al. Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle. Nature 494, 480–483 (2013). https://doi.org/10.1038/nature11897
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