The Sca-1⁺ and Sca-1^- mouse prostatic luminal cell lineages are independently sustained

The phenotypic and functional heterogeneity of the mouse prostate epithelial cell lineages remains incompletely characterized. We show that the Sca-1⁺ luminal cells at the mouse proximal prostate express Sox2. These cells are replicative quiescent, castration resistant, and do not possess secretory function. We use the Probasin-CreER^T2 and Sox2-CreER^T2 models in concert with a fluorescent reporter line to label the Sca-1^- and Sca-1⁺ luminal cells, respectively. By a lineage tracing approach, we show that the two luminal cell populations are independently sustained. Sox2 is dispensable for the maintenance of the Sca-1⁺ luminal cells but is essential for their facultative bipotent differentiation capacity. The Sca-1⁺ luminal cells share molecular features with the human TACSTD2⁺ luminal cells. This study corroborates the heterogeneity of the mouse prostate luminal cell lineage and shows that the adult mouse prostate luminal cell lineage is maintained by distinct cellular entities rather than a single progenitor population.