In situ identification of bipotent stem cells in the mammary gland

Nature. 2014 Feb 20;506(7488):322-7. doi: 10.1038/nature12948. Epub 2014 Jan 26.


The mammary epithelium undergoes profound morphogenetic changes during development. Architecturally, it comprises two primary lineages, the inner luminal and outer myoepithelial cell layers. Two opposing concepts on the nature of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model, based on classical transplantation assays, postulates that bipotent MaSCs have a key role in coordinating ductal epithelial expansion and maintenance in the adult gland, whereas the second model proposes that only unipotent MaSCs identified by lineage tracing contribute to these processes. Through clonal cell-fate mapping studies using a stochastic multicolour cre reporter combined with a new three-dimensional imaging strategy, we provide evidence for the existence of bipotent MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at different developmental stages support a model in which both stem and progenitor cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate ductal homeostasis and remodelling of the mouse adult gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Cell Tracking
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Keratin-14 / metabolism
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Human / cytology*
  • Mice
  • Morphogenesis
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism
  • Puberty
  • Receptors, G-Protein-Coupled / metabolism
  • Sexual Maturation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Elf5 protein, mouse
  • Keratin-14
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Transcription Factors