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Nat Commun. 2017 Dec 11;8(1):2128. doi: 10.1038/s41467-017-02001-5.

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

Bach K1,2,3, Pensa S1,3, Grzelak M2,3, Hadfield J2,3, Adams DJ3,4, Marioni JC5,6,7,8, Khaled WT9,10.

Author information

1
Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.
2
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
3
Cancer Research UK Cambridge Cancer Centre, Cambridge, CB2 0RE, UK.
4
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
5
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK. marioni@ebi.ac.uk.
6
Cancer Research UK Cambridge Cancer Centre, Cambridge, CB2 0RE, UK. marioni@ebi.ac.uk.
7
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1HH, UK. marioni@ebi.ac.uk.
8
European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, CB10 1 SD, UK. marioni@ebi.ac.uk.
9
Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK. wtk22@cam.ac.uk.
10
Cancer Research UK Cambridge Cancer Centre, Cambridge, CB2 0RE, UK. wtk22@cam.ac.uk.

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.

PMID:
29225342
PMCID:
PMC5723634
DOI:
10.1038/s41467-017-02001-5
[Indexed for MEDLINE]
Free PMC Article

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