Different animal cell types have distinctive and characteristic sizes. How a particular cell size is specified by differentiation programs and physiology remains one of the fundamental unknowns in cell biology. In this review we explore the evidence that individual cells autonomously sense and specify their own size. We discuss possible mechanisms by which size sensing and size specification may take place. Finally, we explore the physiological implications of size control. Why is it important that particular cell types maintain a particular size? We develop these questions by examination of current literature and pose the questions that we anticipate will guide this field in the upcoming years.

Biologists have long been concerned about what constrains variation in cell size; yet, progress on this question has been slow and stymied by experimental limitations1. 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, one can calculate full time trajectories of any feature that can be labeled fixed cells, for example levels of phospho-proteins 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.