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 Kaplan, Christopher Ormandy, Ewan K. A. Millar, Sandra O’Toole, Kyuson Yun and Alexander Swarbrick ()
Additional contact information
Simon Junankar: Garvan Institute of Medical Research
Laura A. Baker: Garvan Institute of Medical Research
Daniel L. Roden: Garvan Institute of Medical Research
Radhika Nair: Garvan Institute of Medical Research
Ben Elsworth: Garvan Institute of Medical Research
David Gallego-Ortega: Garvan Institute of Medical Research
Paul Lacaze: Millennium Science Pty Ltd
Aurélie Cazet: Garvan Institute of Medical Research
Iva Nikolic: Garvan Institute of Medical Research
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
Sunil R. Lakhani: UQ Centre for Clinical Research, The University of Queensland
Peter T. Simpson: UQ Centre for Clinical Research, The University of Queensland
Ashwini Raghavendra: UQ Centre for Clinical Research, The University of Queensland
Jodi Saunus: UQ Centre for Clinical Research, The University of Queensland
Jason Madore: UQ Centre for Clinical Research, The University of Queensland
Warren Kaplan: Garvan Institute of Medical Research
Christopher Ormandy: Garvan Institute of Medical Research
Ewan K. A. Millar: Garvan Institute of Medical Research
Sandra O’Toole: Garvan Institute of Medical Research
Kyuson Yun: The Jackson Laboratory
Alexander Swarbrick: Garvan Institute of Medical Research

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7548

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