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.