Bhat-Nakshatri, PoornimaGao, HongyuSheng, LiuMcGuire, Patrick C.Xuei, XiaolingWan, JunLiu, YunlongAlthouse, Sandra K.Colter, AustynSandusky, GeorgeStorniolo, Anna MariaNakshatri, Harikrishna2022-06-092022-06-092021-03-16Bhat-Nakshatri P, Gao H, Sheng L, et al. A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells. Cell Rep Med. 2021;2(3):100219. Published 2021 Mar 16. doi:10.1016/j.xcrm.2021.100219https://hdl.handle.net/1805/29309Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalBreast cancerCell of originEpithelial cell clustersNormal breastsSingle-cell analysesArticle