A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells
Poornima Bhat-Nakshatri, Hongyu Gao, Liu Sheng, Patrick C. McGuire, Xiaoling Xuei, Jun Wan, Yunlong Liu, Sandra K. Althouse, Austyn Colter, George Sandusky, Anna Maria Storniolo, Harikrishna Nakshatri
Abstract
Single-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.
Datasets
1. A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells
Metadata
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Source data
https://cellxgene.cziscience.com/collections/c9706a92-0e5f-46c1-96d8-20e42467f287
Alias names
GSE164898, PMID33763657, PMC7974552
Cite this study
Bhat-Nakshatri, P., Gao, H., Sheng, L., McGuire, P.C., Xuei, X., Wan, J., Liu, Y., Althouse, S.K., Colter, A., Sandusky, G. and Storniolo, A.M., 2021. A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells. Cell Reports Medicine, 2(3). https://doi.org/10.1016/j.xcrm.2021.100219
