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Nat Cell Biol ; 16(10): 942-50, 1-7, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25173976

ABSTRACT

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.


Subject(s)
Epithelial Cells/cytology , Mammary Glands, Animal/cytology , Myocytes, Smooth Muscle/metabolism , Stem Cells/cytology , Actins/metabolism , Animals , Benzamides/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Dioxoles/pharmacology , Epithelial Cells/metabolism , Female , Flow Cytometry , Gene Expression Profiling , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Interleukin Receptor Common gamma Subunit/deficiency , Interleukin Receptor Common gamma Subunit/genetics , Mammary Glands, Animal/metabolism , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred NOD , Mice, SCID , Mice, Transgenic , Microscopy, Fluorescence , Myocytes, Smooth Muscle/cytology , Oligonucleotide Array Sequence Analysis , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Stem Cells/metabolism
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