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Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing.

Published version
Peer-reviewed

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Authors

Bach, Karsten 
Pensa, Sara 
Grzelak, Marta 
Adams, David J 

Abstract

Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells-especially in the luminal compartment-should rather be conceptualised as being part of a continuous spectrum of differentiation. Furthermore, our data support the existence of a common luminal progenitor cell giving rise to intermediate, restricted alveolar and hormone-sensing progenitors. This luminal progenitor compartment undergoes transcriptional changes in response to a full pregnancy, lactation and involution. In summary, our results provide a global, unbiased view of adult mammary gland development.

Description

Keywords

Animals, Cell Differentiation, Cells, Cultured, Epithelial Cells, Female, Gene Ontology, Mammary Glands, Animal, Mice, Inbred C57BL, Sequence Analysis, RNA, Single-Cell Analysis, Stem Cells, Transcriptome

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (17348)
Cancer Research UK (C14303/A17197)
Cancer Research UK (22231)