Figure 3. Model of the differentiation hierarchy within mammary epithelium.

Stem cells negative for ER and PR reside within the basal layer of the mammary gland. Upon initiation of pregnancy, these cells undergo several rounds of proliferation and specification to produce common bipotent progenitor cells that further specified to become luminal specific and basal specific progenitor cells. Luminal progenitors proliferate in response to P4 and E2. However, the ER-, PR-negative but RANK-positive meyoepithelial progenitor cells expand in response to RANKL expressed by luminal progenitor cells.