The mammary stem cell hierarchy.

The mammary epithelium undergoes enormous morphogenetic changes during the lifespan of a mammal. The recent elucidation of an epithelial differentiation hierarchy in the mouse mammary gland through classical transplantation and clonogenic assays has pointed to the existence of multipotent mammary stem cells (MaSCs) and at least two distinct luminal progenitor types. Moreover, an analogous functional hierarchy has been defined in human breast tissue. The existence of slow cycling stem cells, both long- and short-term repopulating cells, and a unique fetal MaSC population, imply a complex stem cell compartment within the mammary gland. The recent discovery of unipotent stem-like cells from lineage tracing studies has added a further layer of complexity to the emerging differentiation hierarchy. Although the precise relationships between stem and progenitor cells have yet to be resolved, the epithelial hierarchy has provided an important framework for elucidating the roles of molecular regulators of mammary gland ontogeny and understanding potential cells of origin in breast cancer.