title: Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle.
abstract: Biologists have long been concerned about what constrains variation in cell size, but progress in this field has been slow and stymied by experimental limitations. 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 state. 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.
authors: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Ran
authors: R
authors: Kafri
authors: Jason
authors: J
authors: Levy
authors: Miriam B
authors: MB
authors: Ginzberg
authors: Seungeun
authors: S
authors: Oh
authors: Galit
authors: G
authors: Lahav
authors: Marc W
authors: MW
authors: Kirschner
mesh_terms: D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size / Q000187:drug effects; D003513:Cycloheximide; D004121:Dimethyl Sulfoxide; D025461:Feedback, Physiological; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins; D010750:Phosphoproteins; D016196:S Phase / Q000502:physiology; D059010:Single-Cell Analysis / Q000379:methods*; D020123:Sirolimus
chemical_list: D007976:Leupeptins; D010750:Phosphoproteins; D003513:Cycloheximide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D020123:Sirolimus; D004121:Dimethyl Sulfoxide