Human keratinocytes have two interconvertible modes of proliferation.
Nat Cell Biol
Springer Science and Business Media LLC
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Roshan, A., Murai, K., Fowler, J., Simons, B., Nikolaidou-Neokosmidou, V., & Jones, P. (2016). Human keratinocytes have two interconvertible modes of proliferation.. Nat Cell Biol, 18 145-156. https://doi.org/10.1038/ncb3282
Single stem cells, including those in human epidermis, have a remarkable ability to reconstitute tissues in vitro, but the cellular mechanisms that enable this are ill-defined. Here we used live imaging to track the outcome of thousands of divisions in clonal cultures of primary human epidermal keratinocytes. Two modes of proliferation were seen. In 'balanced' mode, similar proportions of proliferating and differentiating cells were generated, achieving the 'population asymmetry' that sustains epidermal homeostasis in vivo. In 'expanding' mode, an excess of cycling cells was produced, generating large expanding colonies. Cells in expanding mode switched their behaviour to balanced mode once local confluence was attained. However, when a confluent area was wounded in a scratch assay, cells near the scratch switched back to expanding mode until the defect was closed. We conclude that the ability of a single epidermal stem cell to reconstitute an epithelium is explained by two interconvertible modes of proliferation regulated by confluence.
The initial association of holoclone and paraclone type behaviour in clonal cultures of NFSK with stem and balanced progenitor dynamics was due to BDS working in collaboration with PHJ, VN-N, David Doupé and Allon Klein, based on the quantitative analysis of published and unpublished colony size distributions6 . We thank Gözde Akdeniz & David Doupé for experimental work that led up to the project that was analysed by Allon Klein and Genneth Zhang, Patrick Lombard at the Wellcome TrustMedical Research Council Cambridge Stem Cell Institute for Bioinformatics analysis and Esther Choolun for technical assistance. We acknowledge the support of the Wellcome Trust, Cambridge Cancer Centre, Medical Research Council, the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) and Cancer Research UK (Programme grant C609/A17257).
Medical Research Council (MC_UU_12022/3)
Wellcome Trust (098357/Z/12/Z)
Cancer Research UK (C609/A17257)
Wellcome Trust (090334/Z/09/Z)
External DOI: https://doi.org/10.1038/ncb3282
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252708