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

Author

Listed:
  • Simon Junankar

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Laura A. Baker

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Daniel L. Roden

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Radhika Nair

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Ben Elsworth

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • David Gallego-Ortega

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Paul Lacaze

    (Millennium Science Pty Ltd)

  • Aurélie Cazet

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Iva Nikolic

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Wee Siang Teo

    (Garvan Institute of Medical Research)

  • Jessica Yang

    (Garvan Institute of Medical Research)

  • Andrea McFarland

    (Garvan Institute of Medical Research)

  • Kate Harvey

    (Garvan Institute of Medical Research)

  • Matthew J. Naylor

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW
    Discipline of Physiology and Bosch Institute, School of Medical Sciences, University of Sydney)

  • Sunil R. Lakhani

    (UQ Centre for Clinical Research, The University of Queensland
    School of Medicine, The University of Queensland
    Pathology Queensland, The Royal Brisbane and Women’s Hospital
    QIMR Berghofer Medical Research Institute)

  • Peter T. Simpson

    (UQ Centre for Clinical Research, The University of Queensland
    School of Medicine, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Ashwini Raghavendra

    (UQ Centre for Clinical Research, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Jodi Saunus

    (UQ Centre for Clinical Research, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Jason Madore

    (UQ Centre for Clinical Research, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Warren Kaplan

    (Garvan Institute of Medical Research)

  • Christopher Ormandy

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

  • Ewan K. A. Millar

    (Garvan Institute of Medical Research
    South Eastern Area Laboratory Service, St George Hospital
    School of Medical Sciences, UNSW
    Faculty of Medicine & Health Sciences, University of Western Sydney)

  • Sandra O’Toole

    (Garvan Institute of Medical Research
    Sydpath, St Vincent’s Hospital
    Sydney Medical School, University of Sydney)

  • Kyuson Yun

    (The Jackson Laboratory)

  • Alexander Swarbrick

    (Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, UNSW)

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.

Suggested Citation

  • 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 & K, 2015. "ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7548
    DOI: 10.1038/ncomms7548
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    Cited by:

    1. Xing Yang & Haibo Xu & Xu Yang & Hui Wang & Li Zou & Qin Yang & Xiaopeng Qi & Li Li & Hongxia Duan & Xiyun Yan & Nai Yang Fu & Jing Tan & Zongliu Hou & Baowei Jiao, 2024. "Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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