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

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35 Citations (Scopus)

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
Article number6548
Number of pages12
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Mar 2015
Externally publishedYes

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