Two functionally distinct epithelial progenitors exist within the luminal cell compartment of the mouse mammary gland
© BioMed Central Ltd 2008
Published: 13 May 2008
The organization of the mammary epithelial cell hierarchy is poorly understood.
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.
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-)CD24highCD14+phenotype. This progenitor cell population can be further resolved into two functionally distinct subpopulations based on the expression of Sca1. The Lin-CD24highCD14+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-CD24highCD14-Sca1- alveolar cells during pregnancy. The Lin-CD24highCD14+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-CD24highCD14-Sca1+ phenotype.
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.