Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome

被引:37
作者
Chen, Weiyan [1 ]
Morabito, Samuel J. [2 ]
Kessenbrock, Kai [2 ]
Enver, Tariq [3 ]
Meyer, Kerstin B. [4 ]
Teschendorff, Andrew E. [1 ]
机构
[1] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol,CAS Key Lab Co, 320 Yue Yang Rd, Shanghai 200031, Peoples R China
[2] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, 839 Hlth Sci Rd,Sprague Hall 114 Irvine, Irvine, CA 92697 USA
[3] UCL, UCL Canc Inst, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England
[4] Wellcome Sanger Inst, Cambridge CB10 1SA, England
基金
美国国家科学基金会;
关键词
EXPRESSION; IDENTIFICATION; HETEROGENEITY; PROGENITORS; REGULATORS; ENTROPY; ATLAS; MAPS;
D O I
10.1038/s42003-019-0554-8
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Adult stem-cells may serve as the cell-of-origin for cancer, yet their unbiased identification in single cell RNA sequencing data is challenging due to the high dropout rate. In the case of breast, the existence of a bipotent stem-like state is also controversial. Here we apply a marker-free algorithm to scRNA-Seq data from the human mammary epithelium, revealing a high-potency cell-state enriched for an independent mammary stem-cell expression module. We validate this stem-like state in independent scRNA-Seq data. Our algorithm further predicts that the stem-like state is bipotent, a prediction we are able to validate using FACS sorted bulk expression data. The bipotent stem-like state correlates with clinical outcome in basal breast cancer and is characterized by overexpression of YBX1 and ENO1, two modulators of basal breast cancer risk. This study illustrates the power of a marker-free computational framework to identify a novel bipotent stem-like state in the mammary epithelium.
引用
收藏
页数:13
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