Figure 1

Schematic representation of the WI-38 cell model (adapted from [21]). Schematic representation of the physiological state (young, senescent, immortal, tumorigenic) and introduced modifications (hTERT, H-RAS, p53 inactivation) of the WI-38 cells along the process of malignant transformation. The stages chosen for the theoretical analyses can be arranged as several continuous trajectories where each sample follows the preceding one. A common route for many trajectories, the ones we highlight in the text, is represented by the blue color. The first branching occurs at the point 6 (pale blue) and generates the trajectory 156. The second branching occurs at the point 8 and generates 3 trajectories: 1-5-7-8-10-12 (red), 1-5-7-8-11 (yellow) and 1-5-7-8-9 (purple). There is an additional independent trajectory 1-3-4 (black). PDLs are the number of doublings since the cells primary isolation in vitro.