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.
MeSH terms
-
Actins / metabolism
-
Animals
-
Benzamides / pharmacology
-
Cell Proliferation / drug effects
-
Cells, Cultured
-
Dioxoles / pharmacology
-
Epithelial Cells / cytology*
-
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 / cytology*
-
Mammary Glands, Animal / metabolism
-
Mice, Inbred C57BL
-
Mice, Inbred CBA
-
Mice, Inbred NOD
-
Mice, SCID
-
Mice, Transgenic
-
Microscopy, Fluorescence
-
Myocytes, Smooth Muscle / cytology
-
Myocytes, Smooth Muscle / metabolism*
-
Oligonucleotide Array Sequence Analysis
-
Receptors, Transforming Growth Factor beta / antagonists & inhibitors
-
Receptors, Transforming Growth Factor beta / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Stem Cells / cytology*
-
Stem Cells / metabolism
Substances
-
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
-
Actins
-
Benzamides
-
Dioxoles
-
Il2rg protein, mouse
-
Interleukin Receptor Common gamma Subunit
-
Receptors, Transforming Growth Factor beta
-
Green Fluorescent Proteins