Licensing and competition of stem cells at the niche combine to regulate tissue maintenance

Abstract

To maintain and regenerate adult tissues after injury, the numbers, proliferation, and differentiation rates of tissue-resident stem cells must be precisely regulated. The regulatory strategies preventing exhaustion or overgrowth of the stem cell pool, whether there is coordination between different mechanisms, and how to detect them from snapshots of the cell populations, remains un-resolved. Recent findings in the Drosophila testes show that prior to differentiation, somatic stem cells transition to a state that licenses them to differentiate upon receiving a commitment signal, but remain capable of fully regaining stem cell function. Here, we build stochastic mathematical models for the somatic stem cell population to investigate how licensing contributes to homeostasis and the variability of stem cell numbers. We find that licensing alone is sufficient regulation to maintain a stable homeostatic state and prevent stem cell extinction. Comparison with previous experimental data argues for the likely presence of regulation through competition for niche access. We show that competition for niche access contributes to the reduction of the variability of stem cell numbers but does not prevent extinction. Our results suggest that a combination of both regulation strategies, licensing and competition for niche access, is needed to reduce variability and prevent extinction simultaneously.