1] The Kinghorn Cancer Centre &Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia [2] St Vincent's Clinical School, Faculty of Medicine, UNSW, Kensington, New South Wales 2033, Australia.
Millennium Science Pty Ltd, 4 Miles Street, Mulgrave, Victoria 3170, Australia.
Nat Commun. 2015 Mar 27;6:6548. doi: 10.1038/ncomms7548.
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.
基底样乳腺癌（BLBC）是一种预后不良的异质性疾病，但它的细胞起源和病因尚不清楚。在这项研究中，我们表明分化抑制因子 4（ID4）是乳腺干细胞自我更新的关键调节因子，并标记了具有潜在乳腺基底细胞起源的 BLBC 的一个亚群。使用 ID4GFP 敲入报告小鼠和单细胞转录组学，我们表明 ID4 标记了乳腺基底细胞群体中富含干细胞的亚群。ID4 通过抑制 lumen 分化所需的关键因子来维持乳腺干细胞池。此外，ID4 特异性表达于具有非常差预后和类似于乳腺干细胞转录特征的一部分人类 BLBC 中。这些研究将 ID4 鉴定为乳腺干细胞调节剂，阐明了 BLBC 的异质性，并将乳腺干细胞的一个亚群与 BLBC 的病因联系起来。
