University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Science
  • School of BioSciences
  • School of BioSciences - Research Publications
  • View Item
  • Minerva Access
  • Science
  • School of BioSciences
  • School of BioSciences - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells

    Thumbnail
    Download
    Published version (5.766Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    45
    38
    Author
    Chang, TH-T; Kunasegaran, K; Tarulli, GA; De Silva, D; Voorhoeve, PM; Pietersen, AM
    Date
    2014-01-01
    Source Title
    Breast Cancer Research
    Publisher
    BMC
    University of Melbourne Author/s
    Tarulli, Gerard
    Affiliation
    School of BioSciences
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Chang, T. H. -T., Kunasegaran, K., Tarulli, G. A., De Silva, D., Voorhoeve, P. M. & Pietersen, A. M. (2014). New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells. BREAST CANCER RESEARCH, 16 (1), https://doi.org/10.1186/bcr3593.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256107
    DOI
    10.1186/bcr3593
    Abstract
    INTRODUCTION: Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. METHODS: We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. RESULTS: After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. CONCLUSIONS: Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • School of BioSciences - Research Publications [1092]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors