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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Inhibitor of Differentiation Proteins / genetics*
  • Inhibitor of Differentiation Proteins / metabolism
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / metabolism
  • Mice
  • Neoplasm Transplantation
  • Phenotype
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stem Cells / metabolism*

Substances

  • ID4 protein, human
  • Idb4 protein, mouse
  • Inhibitor of Differentiation Proteins
  • RNA, Messenger