Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive

Nat Cell Biol. 2017 Mar;19(3):164-176. doi: 10.1038/ncb3471. Epub 2017 Feb 13.

Abstract

Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5+ basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5+Tspan8hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5+Tspan8hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects*
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation / drug effects
  • Female
  • Hormones / pharmacology*
  • Humans
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / drug effects
  • Mice
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Hormones