Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing.
Adams, David J
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Bach, K., Pensa, S., Grzelak, M., Hadfield, J., Adams, D. J., Marioni, J., & Khaled, W. (2017). Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing.. Nature communications, 8 (1), 2128. https://doi.org/10.1038/s41467-017-02001-5
The mammary gland is a unique organ as it undergoes most of its development during puberty and adulthood. Characterising the hierarchy of the various mammary epithelial cells and how they are regulated in response to gestation, lactation and involution is important for understanding how breast cancer develops. Recent studies have used numerous markers to enrich, isolate and characterise the different epithelial cell compartments within the adult mammary gland. However, in all of these studies only a handful of markers were used to define and trace cell populations. Therefore, there is a need for an unbiased and comprehensive description of mammary epithelial cells within the gland at different developmental stages. To this end we used single cell RNA sequencing (scRNAseq) to determine the gene expression profile of individual mammary epithelial cells across four adult developmental stages; nulliparous, mid gestation, lactation and post weaning (full natural involution). Our data from 23,184 individual cells identifies 15 distinct mammary epithelial cell populations and allows their hierarchical structure across development to be charted. Interestingly, the effect of gestation and lactation appeared to be more pronounced for some cell types. For example, our analysis revealed a cluster of luminal progenitor cells in post involution glands, which is distinct from progenitors found in nulliparous glands. The data also showed that few clusters could be fully characterised by a single marker gene. We argue instead that the epithelial cells – especially in the luminal compartment – should rather be conceptualized as being part of a continuous spectrum of differentiation. This view highlights the plasticity of the tissue and might help to explain the homeostasis of adult mammary epithelial cells.
Mammary Glands, Animal, Cells, Cultured, Epithelial Cells, Stem Cells, Animals, Mice, Inbred C57BL, Sequence Analysis, RNA, Cell Differentiation, Female, Single-Cell Analysis, Transcriptome, Gene Ontology
Cancer Research UK (C14303/A17197)
Cancer Research UK (17348)
External DOI: https://doi.org/10.1038/s41467-017-02001-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276795
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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