Sca-1^pos cells in the mouse mammary gland represent an enriched progenitor cell population

Mammary epithelium can functionally regenerate upon transplantation. This renewal capacity has been classically ascribed to the function of a multipotent mammary gland stem cell population, which has been hypothesized to be a primary target in the etiology of breast cancer. Several complementary approaches were employed in this study to identify and enrich mammary epithelial cells that retain stem cell characteristics. Using long-term BrdU labeling, a population of label retaining cells (LRCs) that lack expression of differentiation markers has been identified. LRCs isolated from mammary primary cultures were enriched for stem cell antigen-1 (Sca-1) and Hoechst dye-effluxing "side population" properties. Sca-1^pos cells in the mammary gland were localized to the luminal epithelia by using Sca-1^+/GFP mice, were progesterone receptor-negative, and did not bind peanut lectin. Finally, the Sca-1^pos population is enriched for functional stem/progenitor cells, as demonstrated by its increased regenerative potential compared with Sca-1^neg cells when transplanted into the cleared mammary fat pads of host mice.