Spermatogonial subsets proposed as the bona fide stem cells are shown above each of the 3 models. In the classic A_single model (A_s), A_single spermatogonia are homogeneous and share stem cell identity (green), having the capacity for self-maintenance (circular arrows; refs. 3, 4, 66). More recently, models have been proposed arguing for greater plasticity among undifferentiated (A_single→A_al16) spermatogonia, with chain fragmentation representing one possible mechanism by which stemness is maintained or regenerated (5). Although fragmentation has been shown to occur in vivo, its contributions to stem cell maintenance under normal conditions or after chemotherapy/radiation have not been formally established. Our findings that only a subset of A_single spermatogonia expressed PAX7 and that these spermatogonia functioned as stem cells suggests a new A_single subset model, whereby PAX7⁺ spermatogonia are self-maintaining and may sit atop the hierarchy of spermatogenic differentiation. That A_single spermatogonia were heterogeneous and that only a subset functioned as stem cells was also suggested by previous studies (10, 67). If so, then this would suggest that some subset of A_single spermatogonia represent transit-amplifying (TA) intermediates. The number of such transit-amplifying steps between PAX7⁺ A_single and A_pair spermatogonia is unknown. It will be interesting to determine whether ID4 and ERBB3, expressed in A_single spermatogonia, are expressed in overlapping or nonoverlapping subsets of spermatogonia relative to PAX7 (9, 49, 50). Other models are possible, such as ones combining different aspects of these models (i.e., fragmentation with the presence of PAX7⁺ spermatogonia, if fragmentation is confirmed as a functionally significant biological process).