ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype
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.
|Authors||Junankar, S.; Baker, L. A.; Roden, D. L.; Nair, R.; Elsworth, B.; Gallego-Ortega, D.; Lacaze, P.; Cazet, A.; Nikolic, I.; Teo, W. S.; Yang, J.; McFarland, A.; Harvey, K.; Naylor, M. J.; Lakhani, S. R.; Simpson, P. T.; Raghavendra, A.; Saunus, J.; Madore, J.; Kaplan, W.; Ormandy, C.; Millar, E. K.; O'Toole, S.; Yun, K.; Swarbrick, A.;|
|Publisher Name||Nature Communications|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/25813983|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12102|