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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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Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny
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Journal Article
Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny
2016
Overview
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.
The identity and origin of adult mammary stem cells has been much debated. Here, the authors use a stochastic genetic labelling approach, together with optical tissue clearing, to visualize clonal progeny and show that unipotent stem/progenitor cells contribute to adult mammary gland development.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 14/19
/ 64/110
/ 82/51
/ Animals
/ Cell Differentiation - physiology
/ Epithelial Cells - physiology
/ Female
/ Humanities and Social Sciences
/ Labeling
/ Male
/ Mammary Glands, Animal - anatomy & histology
/ Mammary Glands, Animal - diagnostic imaging
/ Mammary Glands, Animal - physiology
/ Mice
/ Science
