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

Author

Listed:
  • Felicity M. Davis

    (University of Cambridge
    School of Pharmacy, The University of Queensland)

  • Bethan Lloyd-Lewis

    (University of Cambridge)

  • Olivia B. Harris

    (University of Cambridge
    WellcomeTrust-Medical Research Council Cambridge Stem Cell Institute, 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
    WellcomeTrust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

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.

Suggested Citation

  • Felicity M. Davis & Bethan Lloyd-Lewis & Olivia B. Harris & Sarah Kozar & Douglas J. Winton & Leila Muresan & Christine J. Watson, 2016. "Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13053
    DOI: 10.1038/ncomms13053
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    Cited by:

    1. Elena Spina & Julia Simundza & Angela Incassati & Anupama Chandramouli & Matthias C. Kugler & Ziyan Lin & Alireza Khodadadi-Jamayran & Christine J. Watson & Pamela Cowin, 2022. "Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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