Skin Stem Cell Hypotheses and Long Term Clone Survival – Explored Using Agent-based Modelling

Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (pr...

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Published inScientific reports Vol. 3; no. 1; p. 1904
Main Authors Li, X., Upadhyay, A. K., Bullock, A. J., Dicolandrea, T., Xu, J., Binder, R. L., Robinson, M. K., Finlay, D. R., Mills, K. J., Bascom, C. C., Kelling, C. K., Isfort, R. J., Haycock, J. W., MacNeil, S., Smallwood, R. H.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 28.05.2013
Nature Publishing Group
Subjects
631/114/2397
631/532/2438
631/532/2441
631/553/2695
Asymmetry
Cell Differentiation
Cell Lineage
Cell Proliferation
Cell self-renewal
Cells, Cultured
Epidermis
Epidermis - cytology
Heterogeneity
Homeostasis
Humanities and Social Sciences
Humans
Hypotheses
Keratinocytes
Keratinocytes - cytology
Models, Biological
multidisciplinary
Offspring
Progenitor cells
Regeneration - physiology
Science
Skin
Skin - cytology
Stem cells
Stem Cells - cytology
Stochasticity
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Summary:Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep01904