From microscopic damage to macroscopic games: a dimensionality reduction of stem cell homeostasis

Abstract Tissues must maintain macroscopic homeostasis despite the continuous microscopic accumulation of cellular damage. Related theoretical models often suffer from a disconnect between microscopic biophysics and macroscopic phenomenological games. Here, we bridge this gap by deriving an exact dimensionality reduction of a physiologically structured partial differential equation (PDE) into a low-dimensional equation. Under the condition of uniform mortality, we mathematically demonstrate that tissue homeostasis operates as an induced Nash equilibrium, where the per-capita net growth rates of stem and differentiated phenotypes perfectly equalize. This reduction yields closed-form algebraic rules, the Ratio and Equalization Laws, that map continuous microscopic state dynamics to measurable macroscopic observables. This work provides a rigorous, predictive mathematical foundation for understanding how fast-renewing tissues filter microscopic noise to sustain macroscopic regenerative capacity.