Mouse Spermatogenic Stem Cells Continually Interconvert between Equipotent Singly Isolated and Syncytial States

The identity and behavior of mouse spermatogenic stem cells have been a long-standing focus of interest. In the prevailing A(s) model,'' stem cell function is restricted to singly isolated (As) spermatogonia. By examining single-cell dynamics of GFR alpha 1+ stem cells in vivo, we evaluate an alternative hypothesis that, through fragmentation, syncytial spermatogonia also contribute to stem cell function in homeostasis. We use live imaging and pulse labeling to quantitatively determine the fates of individual GFR alpha 1+ cells and find that, during steady-state spermatogenesis, the entire GFR alpha 1+ population comprises a single stem cell pool, in which cells continually interconvert between As and syncytial states. A minimal biophysical model, relying only on the rates of incomplete cell division and syncytial fragmentation, precisely predicts the stochastic fates of GFR alpha 1+ cells during steady state and post-insult regeneration. Thus, our results define an alternative and dynamic model for spermatogenic stem cell function in the mouse testis.