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

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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.

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Junankar, S., Baker, L. A., Roden, D. L., Nair, R., Elsworth, B., Gallego-Ortega, D., … Swarbrick, A. (2015). ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nature Communications, 6. https://doi.org/10.1038/ncomms7548

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