Fig. 7: Mathematical modelling links cell crowding to ETV4 ultrasensitivity.
From: ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification
a, Model (solid lines) for hESC colony growth that accurately predicts colony growth and proliferation dynamic. Different colours represent three different colonies. b, Comparison between model and observed spatiotemporal change in cell population density. Solid lines show model prediction and boxplots represent the range of experimentally measured cell population densities at certain distance on days 1, 2, 3 and 4. The three panels illustrate three different colonies with an initial average cell population density C0. The black lines in the middle of the boxes are the median values for each group. The vertical size of the boxes illustrates the interquartile range. Whiskers represent 1.5 × interquartile range. n = 4 regions within a colony for each distance. c,d, Model prediction for integrin activity (c), pFAK and ETV4 (d) transition that occurs at a critical cell population density of ~5,000 cells mm–2. Simulation generated for an example colony with an initial radius of 250 μm and an initial average cell population density 3,000 cells mm–2. e, Critical cell densities for ETV4 inactivation measured across H9 colonies. n = 3 regions within a colony. f, Comparison between model and experimental measurement for ETV4 transition (Fig. 2g). Simulation generated for an example colony with an initial radius of 250 μm and an initial average cell population density 3,000 cells mm–2. n = 168 colonies pooled from three independent experiments. g, Model for spatiotemporal change of population density and radial distribution of ETV4. Scale bar, 600 μm. Simulation generated for an example colony with an initial radius of 250 μm and an initial average cell population density 3,000 cells mm–2. h, ETV4 transition map as a function of space and time.
