Notch Signaling Regulates Mammary Stem Cell Function and Luminal Cell-Fate Commitment

Toula Bouras, Bhupinder Pal, François Vaillant, Gwyndolen Harburg, Marie Liesse Asselin-Labat, Samantha R. Oakes, Geoffrey J. Lindeman, Jane E. Visvader

Research output: Contribution to journalArticle

304 Scopus citations

Abstract

The recent identification of mouse mammary stem cells (MaSCs) and progenitor subpopulations has enhanced the prospect of investigating the genetic control of their lineage specification and differentiation. Here we have explored the role of the Notch pathway within the mammary epithelial hierarchy. We show that knockdown of the canonical Notch effector Cbf-1 in the MaSC-enriched population results in increased stem cell activity in vivo as well as the formation of aberrant end buds, implying a role for endogenous Notch signaling in restricting MaSC expansion. Conversely, Notch was found to be preferentially activated in the ductal luminal epithelium in vivo and promoted commitment of MaSCs exclusively along the luminal lineage. Notably, constitutive Notch signaling specifically targeted luminal progenitor cells for expansion, leading to hyperplasia and tumorigenesis. These findings reveal key roles for Notch signaling in MaSCs and luminal cell commitment and further suggest that inappropriate Notch activation promotes the self-renewal and transformation of luminal progenitor cells.

Original languageEnglish (US)
Pages (from-to)429-441
Number of pages13
JournalCell Stem Cell
Volume3
Issue number4
DOIs
StatePublished - Oct 9 2008

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Keywords

  • SIGNALING
  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Bouras, T., Pal, B., Vaillant, F., Harburg, G., Asselin-Labat, M. L., Oakes, S. R., Lindeman, G. J., & Visvader, J. E. (2008). Notch Signaling Regulates Mammary Stem Cell Function and Luminal Cell-Fate Commitment. Cell Stem Cell, 3(4), 429-441. https://doi.org/10.1016/j.stem.2008.08.001