title: ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype.
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.
authors: 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.
authors: Simon
authors: S
authors: Junankar
authors: 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.
authors: Laura A
authors: LA
authors: Baker
authors: 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.
authors: Daniel L
authors: DL
authors: Roden
authors: 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.
authors: Radhika
authors: R
authors: Nair
authors: 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.
authors: Ben
authors: B
authors: Elsworth
authors: 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.
authors: David
authors: D
authors: Gallego-Ortega
authors: Millennium Science Pty Ltd, 4 Miles Street, Mulgrave, Victoria 3170, Australia.
authors: Paul
authors: P
authors: Lacaze
authors: 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.
authors: Aurélie
authors: A
authors: Cazet
authors: 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.
authors: Iva
authors: I
authors: Nikolic
authors: The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors: Wee Siang
authors: WS
authors: Teo
authors: The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors: Jessica
authors: J
authors: Yang
authors: The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors: Andrea
authors: A
authors: McFarland
authors: The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors: Kate
authors: K
authors: Harvey
authors: 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.
authors: Matthew J
authors: MJ
authors: Naylor
authors: 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.
authors: Sunil R
authors: SR
authors: Lakhani
authors: 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.
authors: Peter T
authors: PT
authors: Simpson
authors: 1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
authors: Ashwini
authors: A
authors: Raghavendra
authors: 1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
authors: Jodi
authors: J
authors: Saunus
authors: 1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
authors: Jason
authors: J
authors: Madore
authors: The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors: Warren
authors: W
authors: Kaplan
authors: 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.
authors: Christopher
authors: C
authors: Ormandy
authors: 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.
authors: Ewan K A
authors: EK
authors: Millar
authors: 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.
authors: Sandra
authors: S
authors: O'Toole
authors: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors: Kyuson
authors: K
authors: Yun
authors: 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.
authors: Alexander
authors: A
authors: Swarbrick
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*
chemical_list: C490128:ID4 protein, human; C086479:Idb4 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D012333:RNA, Messenger