The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer landscapes

  1. Jeffrey M Rosen
  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, DeBakey Building M638, Houston, Texas 77030, USA
  1. Correspondence should be addressed to J M Rosen; Email: jrosen{at}
  1. Figure 1

    Schematic illustration of the mammary epithelial cell hierarchy in a developmental context. (A) This panel illustrates the three critical stages in the ontogeny of the mammary epithelium. (i) The mammary gland begins development as an invaginated bud in the embryo. Upon the onset of puberty, (iii) terminal end buds (TEBs) drive the rapid expansion of (ii) ductal structures through the fat in a proliferation-dependent manner. TEBs (iii) comprise an outer layer of cap cells and multilayered body cells that are thought to largely give rise to basal and luminal cells respectively. During pregnancy, (iv) the epithelium proliferates and expands to form grape-like clusters of alveoli that secrete milk during lactation. Magnified snapshots of the (i) embryonic bud, (ii) ductal, (iii) TEB and (iv) alveolar structures indicate the complex and rapidly dynamic cellular compositions during different stages of mammary development. (B) The cells observed spatially in their epithelial context in (A) are displayed based on their position in the epithelial stem cell hierarchy as gleaned from lineage-tracing data. Multipotent progenitors in the embryonic bud differentiate to generate all the mature mammary lineages. In the adult, ducts comprise of basal and luminal lineages. Lineage-tracing data have identified cells in the basal compartment with bipotential capacity, i.e., the ability to give rise to both basal and luminal lineages. More recently, novel Notch2+ luminal populations were described whose origin and function remain ambiguous. Finally, studies in multiparous mice have identified long-lived progenitors termed parity-induced mammary epithelial cells (PI-MECs) that are capable of initiating multiple rounds of alveologenesis during repeated pregnancies. Dotted lines indicate hypothesized derivative cell lineages in the epithelial hierarchy.

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