Developmental Lineage of Mammary Gland Myoepithelial Cells

Myoepithelial cells, which originate from myoepithelial progenitors, are located between luminal cells that line the mammary ducts and alveoli, and the basement membrane (reviewed in Stingl et al. 2005). Myoepithelial cells form a continuous sheath around the ducts but are sparser around the alveoli, where their cytoplasmic processes create a basket-like structure that allows some luminal cells to come in contact with the basement membrane (reviewed in Stingl et al. 2005). Myoepithelial cells are spindle shaped and are able to contract in response to oxytocin, which is necessary for milk secretion (lactation) (reviewed in Stingl et al. 2005, and Watson and Khaled 2020).

Upon ablation of the luminal epithelial cells in the adult mouse mammary gland, unipotent myoepithelial progenitor cells can convert into unipotent luminal progenitors to repopulate the luminal lineage (Centonze et al. 2020, reviewed in Edwards and Brennan 2021). In mouse mammary glands, tumor necrosis factor (TNF), secreted by luminal cells, restricts multipotency of myoepithelial progenitors under normal physiological conditions. After ablation of luminal cells, Notch, Wnt and EGFR signaling pathways are activated in myoepithelial progenitor cells, promoting regeneration-induced multipotency of myoepithelial progenitors (Centonze et al. 2020, reviewed in Edwards and Brennan 2021). In human mammary organoids, high intensity EGFR signaling promotes myoepithelial cell fate. FGF2 and FGF7 are not necessary for the differentiation of myoepithelial cells in human mammary organoids, but they are needed for the establishment of proper architecture of mammary ducts.