Jaba Tkemaladze
The hierarchical organization of stem cell potency—from totipotency to terminal differentiation—lacks a formal quantitative framework linking it to subcellular aging. Here, we propose that cellular potency can be described as a coordinate, χ_Ze, within a Ze-state space—a theoretical continuum defined by the dynamic balance of T-events (anabolic, constructive processes) and S-events (catabolic, degradative processes). We posit that centriolar damage, D(t), accumulated over cell cycles, is the principal driver of χ_Ze in rapidly dividing stem and progenitor cells. Using a sigmoidal (logistic) function χ_Ze(D) = 1 / (1 + exp(-k(D - D₀))), we map known potency states onto a continuous landscape. The classical asymmetry of stem cell division (mother/daughter asymmetry) emerges as a divergence in χ_Ze values between daughter cells, directly regulated by the asymmetric inheritance of centriolar damage. We derive the asymmetry fidelity parameter P_A from first principles via a probabilistic mechanism of centriolar segregation error (p_mis = α·D), yielding P_A = P₀·exp(-α·D). A kinetic equation dD/dt = r - k_rep·D is introduced, and an operational index D_obs = (N_acentriolar + N_amplified) / N_total mitoses · (1/D_max) is proposed for empirical validation. The model predicts that hypoxic niches maintain low χ_Ze by reducing r, that reprogramming (iPSC) reverses χ_Ze, and that cancer stem cells may arise from a stochastic collapse of χ_Ze regulation. Positive feedback loops (damage → mitotic errors → further damage) are discussed as drivers of gerontological transitions.