Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages

Chunhui Wang, John R. Christin, Maja H. Oktay, Wenjun Guo

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER+) and ER luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER+ luminal cells. Both SOX9+ and PROM1+ cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER+ and ER luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.

Original languageEnglish (US)
Pages (from-to)2825-2835
Number of pages11
JournalCell Reports
Issue number12
StatePublished - Mar 21 2017


  • breast cancer
  • cancer cell-of-origin
  • estrogen receptor negative cancer
  • estrogen receptor positive cancer
  • lineage tracing
  • mammary differentiation
  • mammary gland development
  • mammary gland regeneration
  • mammary stem cells
  • stem cell hierarchy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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