| Literature DB >> 25813983 |
Simon Junankar1, Laura A Baker1, Daniel L Roden1, Radhika Nair1, Ben Elsworth1, David Gallego-Ortega1, Paul Lacaze2, Aurélie Cazet1, Iva Nikolic1, Wee Siang Teo3, Jessica Yang3, Andrea McFarland3, Kate Harvey3, Matthew J Naylor4, Sunil R Lakhani5, Peter T Simpson6, Ashwini Raghavendra7, Jodi Saunus7, Jason Madore7, Warren Kaplan3, Christopher Ormandy1, Ewan K A Millar8, Sandra O'Toole9, Kyuson Yun10, Alexander Swarbrick1.
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.Entities:
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Year: 2015 PMID： 25813983 DOI： 10.1038/ncomms7548
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919