Two functionally distinct epithelial progenitors exist within the luminal cell compartment of the mouse mammary gland

Background

The organization of the mammary epithelial cell hierarchy is poorly understood.

Methods

To determine the cells that make up this hierarchy and the relationship between them, we used fluorescence-activated cell sorting in combination with in vitro colony-forming cell assays to examine the growth and differentiative properties of phenotypically distinct subsets of mouse mammary epithelial cells.

Results

Our results indicate that >95% of all colony-forming cells present within the mammary epithelium are localized within the luminal cell compartment and that >90% of these have a CD45^-Ter119^-CD31^-(Lin^-)CD24^highCD14⁺phenotype. This progenitor cell population can be further resolved into two functionally distinct subpopulations based on the expression of Sca1. The Lin^-CD24^highCD14⁺Sca1^- progenitors, which express low levels of estrogen receptor alpha and intermediate levels of keratin 14 (K14), are perceived to be progenitors that produce Lin^-CD24^highCD14^-Sca1^- alveolar cells during pregnancy. The Lin^-CD24^highCD14⁺Sca1⁺ progenitors, which express intermediate levels of estrogen receptor alpha and are K14^-, are perceived to be precursors of the steroid receptor expressing cells, of which the vast majority are terminally differentiated and have a Lin^-CD24^highCD14^-Sca1⁺ phenotype.

Conclusion

These results demonstrate the existence of two functionally distinct progenitor cells within the luminal compartment of the mammary gland and provide a framework for interpreting breast tumour gene expression profiles and the possible origins of breast tumours.