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

Research output: Contribution to journalArticle

35 Scopus citations

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 (US)
Pages (from-to)6548
JournalNature Communications
Volume6
DOIs
StatePublished - Mar 27 2015

Keywords

  • Animals
  • Breast Neoplasms
  • Cell Line, Tumor
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Inhibitor of Differentiation Proteins
  • Mammary Glands, Animal
  • Mice
  • Neoplasm Transplantation
  • Phenotype
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Stem Cells
  • Journal Article
  • Research Support, Non-U.S. Gov't

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