CCAAT/enhancer binding protein beta regulates stem cell activity and specifies luminal cell fate in the mammary gland

Heather L. LaMarca, Adriana P. Visbal, Chad J. Creighton, Hao Liu, Yiqun Zhang, Fariba Behbod, Jeffrey M. Rosen

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The bZIP transcription factor C/EBPβ is important for mammary gland development and its expression is deregulated in human breast cancer. To determine whether C/ EBPβ regulates mammary stem cells (MaSCs), we employed two different knockout strategies. Using both a germline and a conditional knockout strategy, we demonstrate that mammosphere formation was significantly decreased in C/EBPβ-deficient mammary epithelial cells (MECs). Functional limiting dilution transplantation assays indicated that the repopulating ability of C/EBPβ-deleted MECs was severely impaired. Serial transplantation experiments demonstrated that C/EBPβ deletion resulted in decreased outgrowth potential and premature MaSC senescence. In accord, fluorescence-activated cell sorting analysis demonstrated that C/EBPβ-null MECs contained fewer MaSCs, the loss of luminal progenitors and an increase in differentiated luminal cells as compared with wild-type. Gene profiling of C/EBPβ-null stem cells revealed an alteration in cell fate specification, exemplified by the expression of basal markers in the luminal compartment. Thus, C/EBPβ is a critical regulator of both MaSC repopulation activity and luminal cell lineage commitment. These findings have critical implications for understanding both stem cell biology and the etiology of different breast cancer subtypes.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalSTEM CELLS
Volume28
Issue number3
DOIs
StatePublished - Mar 31 2010

Keywords

  • Alveolar
  • C/EBP beta
  • Differentiation
  • Lineage commitment
  • Luminal
  • Mammary stem cell
  • Progenitor cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'CCAAT/enhancer binding protein beta regulates stem cell activity and specifies luminal cell fate in the mammary gland'. Together they form a unique fingerprint.

Cite this