The hierarchical relationships between stem cells, lineage-committed progenitors, and differentiated cells remain unclear in several tissues, due to a high degree of cell plasticity, allowing cells to switch between different cell states. The mouse mammary gland, similarly to other tissues such as the prostate, the sweat gland, and the respiratory tract airways, consists of an epithelium exclusively maintained by unipotent progenitors throughout adulthood. Such unipotent progenitors, however, retain a remarkable cellular plasticity, as they can revert to multipotency during epithelial regeneration as well as upon oncogene activation. Here, we revise the current knowledge on mammary cell hierarchies in light of the most recent lineage tracing studies performed in the mammary gland and highlight how stem cell differentiation or reversion to multipotency are at the base of tumor development and progression. In addition, we will discuss the current knowledge about the interplay between tumor cells of origin and defined genetic mutations, leading to different tumor types, and its implications in choosing specific therapeutic protocols for breast cancer patients.
Keywords: breast cancer; cellular plasticity; lineage tracing; mammary gland; multipotency; stem cells.