Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity

Quy H. Nguyen, Nicholas Pervolarakis, Kerrigan Blake, Dennis Ma, Ryan Tevia Davis, Nathan James, Anh T. Phung, Elizabeth Willey, Raj Kumar, Eric Jabart, Ian Driver, Jason Rock, Andrei Goga, Seema A. Khan, Devon A. Lawson, Zena Werb*, Kai Kessenbrock

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

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 languageEnglish (US)
Article number2028
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - 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

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