Receptor activator of NF-κB ligand promotes proliferation of a putative mammary stem cell unique to the lactating epithelium

Elizabeth Thomas, Tracey F. Lee-Pullen, Paul Rigby, Peter E Hartmann, Jiake Xu, Nikolajs Zeps

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)


In mice, CD49fhi mammary stem cells (MaSCs) asymmetrically divide to generate CD49f+ committed progenitor cells that differentiate into CD49f- phenotypes of the milk-secreting tissue at the onset of pregnancy. We show CD49f+ primary mammary epithelial cells (PMECs) isolated from lactating tissue uniquely respond to pregnancyassociated hormones (PAH) compared with CD49f+ cells from nonlactating tissue. Differentiation of CD49f+ PMEC in extracellular matrix produces CD49f- luminal cells to form differentiated alveoli. The PAH prolactin and placental lactogen specifically stimulate division of CD49f- luminal cells, while receptor activator of nuclear factor (NF)- κB ligand (RANKL) specifically stimulates division of basal CD49f+ cells. In nondifferentiating conditions, we observed a greater proportion of multipotent self-renewing cells, and RANKL treatment activated the RANK pathway in these cultures. Furthermore, we observed the deposition of calcium nodules in a proportion of these cells. These data imply that a MaSC unique to the lactating breast exists in humans, which generates progeny with discrete lineages and distinct response to PAH.

Original languageEnglish
Pages (from-to)1255-1264
Number of pages10
JournalStem Cells
Issue number6
Publication statusPublished - Jun 2012
Externally publishedYes


  • Differentiation
  • Hormones
  • Mammary gland
  • Progenitor cell
  • Receptor activator of NF-κb ligand
  • Stem cell

Cite this