Abstract
Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer.
Original language | English (US) |
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Article number | 2028 |
Journal | Nature communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2018 |
Funding
We thank Ying Yu for technical assistance and animal handling. We are grateful to the Cooperative Human Tissue Network (CHTN) for providing the mammoplasty samples, and to Laura van’t Veer and Denise Wolf for helpful advice on data analysis. This study was supported by funds from the National Cancer Institute (R01 CA057621 and U01 CA199315 to Z.W, R00 CA181490 to K.K., and K22 CA190511 to D.A.L.) and from the Chan/Zuckerberg Initiative (HCA-A-1704-01668 to K.K. and D.A.L.).
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy