Loss of Pten triggers asymmetric division and increases the differentiation-associated proliferation of SSCs. a Whole-mount triple-immunofluorescence of GFRα1, PLZF and UTF1 in seminiferous tubules at 7 days old. In the Pten
+/+ tubules (upper panel), a pair of SSCs (arrows) consisting of one GFRα1+/PLZF+/UTF1low cell and the other GFRα1+/PLZF−/UTF1+ (with UTF1 on the chromatin, arrow) cell was observed, which may undergo an asymmetric division of the stem cell. Meanwhile, a pair of GFRα1−/PLZF−/UTF1+ progeny (arrows) with UTF1 on chromatin was observed in the completing division in the Pten
−/− seminiferous tubules (lower panel) (scale bar is 20 µm). b Whole-mount triple-immunofluorescence of GFRα1, PLZF and UTF1 in Pten
−/− seminiferous tubules at 7 days old showing a group (marked in square) of GFRα1−/PLZF−/UTF1+ cells (purple arrow) next to GFRα1+/PLZF−/UTF1+ cells (yellow arrow) within the context of GFRα1+/PLZF+/UTF1+ SSCs. c A schematic diagram showing a hypothesis of asymmetric division of SSC in the testis at 7 days old. GFRα1+/PLZF+/UTF1+ stem cell underwent a division and gave rise to a GFRα1+/PLZF−/UTF1+ progeny, which in turn divided into two GFRα1−/PLZF−/UTF1+ cells towards differentiation fate. Loss of Pten accelerated this pathway and disturbed the balance of self-renewal versus differentiation of GFRα1+/PLZF+/UTF1+ stem cells, thereby causing SSCs depletion and infertility with age.