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 () and Kai Kessenbrock ()
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Quy H. Nguyen: University of California, Irvine
Nicholas Pervolarakis: Center for Complex Biological Systems, University of California, Irvine
Kerrigan Blake: Center for Complex Biological Systems, University of California, Irvine
Dennis Ma: University of California, Irvine
Ryan Tevia Davis: University of California, Irvine
Nathan James: University of California, Irvine
Anh T. Phung: University of California, Irvine
Elizabeth Willey: University of California
Raj Kumar: University of California
Eric Jabart: ProteinSimple, 3001 Orchard Parkway
Ian Driver: University of California
Jason Rock: University of California
Andrei Goga: University of California
Seema A. Khan: Feinberg School of Medicine, Northwestern University
Devon A. Lawson: University of California, Irvine
Zena Werb: University of California
Kai Kessenbrock: University of California, Irvine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04334-1

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DOI: 10.1038/s41467-018-04334-1

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