Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny

Felicity M. Davis, Bethan Lloyd-Lewis, Olivia B. Harris, Sarah Kozar, Douglas J. Winton, Leila Muresan and Christine J. Watson ()
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Felicity M. Davis: University of Cambridge
Bethan Lloyd-Lewis: University of Cambridge
Olivia B. Harris: University of Cambridge
Sarah Kozar: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Douglas J. Winton: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Leila Muresan: Cambridge Advanced Imaging Centre, University of Cambridge
Christine J. Watson: University of Cambridge

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.

Date: 2016
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DOI: 10.1038/ncomms13053

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