Kinetic energy flux (KEF). Global perturbation of the genome engine is well-manifested in the kinetic energy flux (Section 4.2.4) for single-cell responses in (A) embryo development and (B) immune cells, and population responses in (C) MCF-7 cells and (d) HL-60 cells. At the single-cell level, the timing of global perturbation, with the involvement of more than one critical state, coincides with that of the cell-fate change (Figure 7, Figure 8 and Figure 9). At the population level, kinetic energy flux is damping. In HRG-stimulated MCF-7 cells (C), the timing of the activation of the CP (ON at 15 min; Figure 4A: left panel) is within the global perturbation (10–30 min) (intersection of interaction flux at 20–30 min: Figure 14A), whereas in EGF stimulation (right panel; no cell differentiation [29]), only local perturbation occurs. On the other hand, in HL-60 cells (D), the timing of the perturbation of the genome engine (at 18 h, 24 h and 48 h) corresponds to the end of the damping (second-largest perturbation) for atRA-stimulated HL-60 cells (left panel) and the largest global perturbation (at 12 h, 18 h, and 24 h) for DMSO-stimulated HL-60 cells (right panel). Underlined numbers represent the timing just before the cell-fate change.