ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype

Simon Junankar, Laura A Baker, Daniel L Roden, Radhika Nair, Ben Elsworth, David Gallego-Ortega, Paul Lacaze, Aurélie Cazet, Iva Nikolic, Wee Siang Teo, Jessica Yang, Andrea McFarland, Kate Harvey, Matthew J Naylor, Sunil R Lakhani, Peter T Simpson, Ashwini Raghavendra, Jodi Saunus, Jason Madore, Warren KaplanChristopher Ormandy, Ewan K A Millar, Sandra O'Toole, Kyuson Yun, Alexander Swarbrick

    Research output: Contribution to journalArticlepeer-review

    48 Scopus citations

    Abstract

    Basal-like breast cancer (BLBC) is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative mammary basal cell of origin. Using an ID4GFP knock-in reporter mouse and single-cell transcriptomics, we show that ID4 marks a stem cell-enriched subset of the mammary basal cell population. ID4 maintains the mammary stem cell pool by suppressing key factors required for luminal differentiation. Furthermore, ID4 is specifically expressed by a subset of human BLBC that possess a very poor prognosis and a transcriptional signature similar to a mammary stem cell. These studies identify ID4 as a mammary stem cell regulator, deconvolute the heterogeneity of BLBC and link a subset of mammary stem cells to the aetiology of BLBC.

    Original languageEnglish (US)
    Pages (from-to)6548
    JournalNature Communications
    Volume6
    DOIs
    StatePublished - Mar 27 2015

    Keywords

    • Animals
    • Breast Neoplasms
    • Cell Line, Tumor
    • Female
    • Gene Knock-In Techniques
    • Humans
    • Inhibitor of Differentiation Proteins
    • Mammary Glands, Animal
    • Mice
    • Neoplasm Transplantation
    • Phenotype
    • RNA, Messenger
    • Real-Time Polymerase Chain Reaction
    • Stem Cells
    • Journal Article
    • Research Support, Non-U.S. Gov't

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