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

    Access Status
    Open access via publisher
    Authors
    Thomas, E.
    Lee-Pullen, T.
    Rigby, P.
    Hartmann, P.
    Xu, J.
    Zeps, Nikolajs
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Thomas, E. and Lee-Pullen, T. and Rigby, P. and Hartmann, P. and Xu, J. and Zeps, N. 2012. Receptor activator of NF-κB ligand promotes proliferation of a putative mammary stem cell unique to the lactating epithelium. Stem Cells. 30 (6): pp. 1255-1264.
    Source Title
    Stem Cells
    DOI
    10.1002/stem.1092
    ISSN
    1066-5099
    URI
    http://hdl.handle.net/20.500.11937/45110
    Collection
    • Curtin Research Publications
    Abstract

    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 pregnancy-associated 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.

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