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

Karsten Bach, Sara Pensa, Marta Grzelak, James Hadfield, David J. Adams, John C. Marioni () and Walid T. Khaled ()
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Karsten Bach: University of Cambridge
Sara Pensa: University of Cambridge
Marta Grzelak: University of Cambridge
James Hadfield: University of Cambridge
David J. Adams: Cancer Research UK Cambridge Cancer Centre
John C. Marioni: University of Cambridge
Walid T. Khaled: University of Cambridge

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-02001-5

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