Mammary stem cells have myoepithelial cell properties

• DOI: 10.1038/ncb3025
• Publication Date: 2014-08-31T19:28:57Z
• Authors: Michael D. Prater; Valérie Petit; I. Alasdair Russell; Rajshekhar R. Gir...; Mona Shehata; Suraj Menon; Reiner Schulte; Ivo Kalajzic; Nicola Rath; Michael F. Olson; Daniel Metzger; Marisa M. Faraldo; Marie-Ange Deugnier; Marina A. Glukhova; John Stingl
• Keywords: Green Fluorescent Proteins; Myocytes, Smooth Muscle; Mice, Transgenic; Dioxoles; Mice, SCID; Article; 03 medical and health sciences; Mammary Glands, Animal; Mice, Inbred NOD; Animals; Cells, Cultured; Oligonucleotide Array Sequence Analysis; Cell Proliferation; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Gene Expression Profiling; Epithelial Cells; Flow Cytometry; Actins; Mice, Inbred C57BL; Microscopy, Fluorescence; Benzamides; Mice, Inbred CBA; Female; Receptors, Transforming Growth Factor beta; Interleukin Receptor Common gamma Subunit

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt actin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using two independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage-tracing approach we follow the progeny of myoepithelial cells that express α-smooth muscle actin and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy.