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

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  • Felicity M. Davis
  • Bethan Lloyd-Lewis, University of Cambridge
  • ,
  • Olivia B. Harris, University of Cambridge
  • ,
  • Sarah Kozar, University of Cambridge
  • ,
  • Douglas J. Winton, University of Cambridge
  • ,
  • Leila Muresan, Cambridge Advanced Imaging Centre
  • ,
  • Christine J. Watson, University of Cambridge

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.

Original languageEnglish
Article number13053
JournalNature Communications
Publication statusPublished - 25 Oct 2016
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Department of Pathology Biological Services Unit for help with animal work, H. Skelton for help with histology and Peter Humphreys and Dr Martin Lenz for imaging support. This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (B.L-L. and C.J.W). F.M.D. was funded by a National Health and Medical Research Council CJ Martin Biomedical Fellowship (GNT1071074). O.B.H. was funded by a Wellcome Trust PhD studentship (105377/Z/14/Z).

Publisher Copyright:
© 2016 The Author(s).

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