Epithelial Stem Cells in the Murine Prostate
With respect to the location of epithelial stem cells within the prostate gland, different results have been obtained using the mouse model. Unlike the human prostate, the murine organ can be subdivided into ventral and dorsolateral prostates, which in turn consist of ventral and dorsolateral lobes. Individual ducts are made up of proximal, intermediate, and distal regions. Label-retention studies on mice demonstrated that the majority of quiescent cells are located in the proximal region of the ducts, whereas luminal cells are located at the ductal tips. Label retention is a common method of mapping the location of stem cells, which is based on the assumption that cells exhibiting stem cell properties will enter the cell cycle very infrequently and therefore retain a DNA label for an extended period of time. In contrast, label density will decrease rapidly in actively dividing cells. Interestingly, label-retaining cells in the mouse prostate are located among both the basal and luminal cells in the proximal region, which either suggests that basal and luminal cells in the murine prostate form separate lineages or that label-retaining cells in the luminal compartment constitute an early transit-amplifying population derived from basal stem cells. Proximal, label-retaining cells have a higher proliferative potential than that of distal cells in vitro and are capable of forming large glandular structures in collagen gels, which is in accordance with a stem cell phenotype. Burger et al. enriched for murine prostate epithelial stem cells from the proximal region of prostatic ducts on the basis of expression of Sca-1 (stem cell antigen 1). The Sca-1-purified cells efficiently regenerated prostatic ducts in vivo and expressed a6-integrin as well as the antiapoptotic marker bcl-2, which is commonly expressed among stem cells. Xin et al. enriched for Sca-1-expressing cells from murine prostate by flow-sorting and demonstrated prostate-regenerating activity for the subpopulation selected. Lawson et al. went on to show that Sca-1 expression in cells in the proximal murine duct region co-localizes with both basal (cytokeratin 5) and luminal (cytokeratin 
cytokeratins, which implies that Sca-1 expression is not restricted to the stem cell population but might be retained by early progenitor cells, which could be the luminal-like label retaining cells proposed by Tsujimura et al.
