title: Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.
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.
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|School of Pharmacy, The University of Queensland, Brisbane 4072, Australia.
authors: Felicity M
authors: FM
authors: Davis
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Bethan
authors: B
authors: Lloyd-Lewis
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|WellcomeTrust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
authors: Olivia B
authors: 0000-0002-2641-6472
authors: OB
authors: Harris
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
authors: Sarah
authors: S
authors: Kozar
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
authors: Douglas J
authors: DJ
authors: Winton
authors: Cambridge Advanced Imaging Centre, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Leila
authors: 0000-0002-7602-0249
authors: L
authors: Muresan
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.|WellcomeTrust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
authors: Christine J
authors: 0000-0002-8548-5902
authors: CJ
authors: Watson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002999:Clone Cells / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D004848:Epithelium / Q000502:physiology*; D005260:Female; D021621:Imaging, Three-Dimensional; D008297:Male; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D023421:Models, Animal; D038081:Organogenesis / Q000502:physiology*; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000502:physiology*