ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype.
Nat Commun 2015 Mar 27; 6:6548.
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. Nat Commun 2015 Mar 27; 6:6548.
Junankar, Simon; Baker, Laura A; Roden, Daniel L; Nair, Radhika; Elsworth, Ben; Gallego-Ortega, David; Lacaze, Paul; Cazet, Aurélie; Nikolic, Iva; Teo, Wee Siang; Yang, Jessica; McFarland, Andrea; Harvey, Kate; Naylor, Matthew J; Lakhani, Sunil R; Simpson, Peter T; Raghavendra, Ashwini; Saunus, Jodi; Madore, Jason; Kaplan, Warren; Ormandy, Christopher; Millar, Ewan K A; O'Toole, Sandra; Yun, Kyuson; and Swarbrick, Alexander, "ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype." (2015). Faculty Research 2015. 58.