Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis

To clarify the mechanisms that support the continuity of actively cycling tissues of long-lived organisms, we investigated the composition of a mouse spermatogenic stem cell system by pulse-chase of the undifferentiated spermatogonia, the population responsible for stem cell functions, in combination with transplantation and regeneration assays after pulse-labeling. We demonstrate that in addition to "actual stem cells," which are indeed self-renewing, a second population ("potential stem cells") also exists, which is capable of self-renewing but do not self-renew in the normal situation. Potential stem cells rapidly turn over in normal testes, suggesting that they belong to the transit-amplifying, rather than the dormant, population. During the long natural course, actual stem cells are occasionally lost and compensated for by progeny of their neighbors. In this process, potential stem cells are postulated to shift their modes from transit amplification to self-renewal, thus playing an essential role to ensure spermatogenesis integrity.