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Nat Commun. 2015 Mar 27;6:6548. doi: 10.1038/ncomms7548.

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

Author information

1
1] The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia [2] St Vincent's Clinical School, Faculty of Medicine, UNSW, Kensington, New South Wales 2033, Australia.
2
Millennium Science Pty Ltd, 4 Miles Street, Mulgrave, Victoria 3170, Australia.
3
The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
4
1] The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia [2] St Vincent's Clinical School, Faculty of Medicine, UNSW, Kensington, New South Wales 2033, Australia [3] Discipline of Physiology and Bosch Institute, School of Medical Sciences, University of Sydney, Camperdown, New South Wales 2006, Australia.
5
1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] School of Medicine, The University of Queensland, Brisbane, Queensland 4072, Australia [3] Pathology Queensland, The Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia [4] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
6
1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] School of Medicine, The University of Queensland, Brisbane, Queensland 4072, Australia [3] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
7
1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
8
1] The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia [2] Department of Anatomical Pathology, South Eastern Area Laboratory Service, St George Hospital, Kogarah, New South Wales 2217, Australia [3] School of Medical Sciences, UNSW, Kensington, New South Wales 2033, Australia [4] Faculty of Medicine &Health Sciences, University of Western Sydney, Campbelltown, New South Wales 2560, Australia.
9
1] The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia [2] Department of Anatomical Pathology, Sydpath, St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia [3] Sydney Medical School, University of Sydney, Camperdown, New South Wales 2006, Australia.
10
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.

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.

PMID:
25813983
DOI:
10.1038/ncomms7548
[Indexed for MEDLINE]

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