Mammary Stem Cells Have Myoepithelial Cell Properties

Nat Cell Biol. 2014 Oct;16(10):942-50, 1-7. doi: 10.1038/ncb3025. Epub 2014 Aug 31.

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

Associated data

  • GEO/GSE31347