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Nat Commun. 2018 May 23;9(1):2028. doi: 10.1038/s41467-018-04334-1.

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

Author information

1
Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA.
2
Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, 92697, USA.
3
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, 92697, USA.
4
Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA, 94143-0452, USA.
5
ProteinSimple, 3001 Orchard Parkway, San Jose, CA, 95134, USA.
6
Department of Cell and Tissue Biology, University of California, San Francisco, CA, 94143-0452, USA.
7
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
8
Department of Anatomy and Biomedical Sciences Program, University of California, San Francisco, CA, 94143-0452, USA. zena.werb@ucsf.edu.
9
Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA. kai.kessenbrock@uci.edu.

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.

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