title: Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.
abstract: 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.
authors.affiliation: Department of Computer Science, University of Sheffield, Sheffield, United Kingdom. xinshan.li@sheffield.ac.uk
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: A K
authors.initials: AK
authors.lastname: Upadhyay
authors.forename: A J
authors.initials: AJ
authors.lastname: Bullock
authors.forename: T
authors.initials: T
authors.lastname: Dicolandrea
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: R L
authors.initials: RL
authors.lastname: Binder
authors.forename: M K
authors.initials: MK
authors.lastname: Robinson
authors.forename: D R
authors.initials: DR
authors.lastname: Finlay
authors.forename: K J
authors.initials: KJ
authors.lastname: Mills
authors.forename: C C
authors.initials: CC
authors.lastname: Bascom
authors.forename: C K
authors.initials: CK
authors.lastname: Kelling
authors.forename: R J
authors.initials: RJ
authors.lastname: Isfort
authors.forename: J W
authors.initials: JW
authors.lastname: Haycock
authors.forename: S
authors.initials: S
authors.lastname: MacNeil
authors.forename: R H
authors.initials: RH
authors.lastname: Smallwood
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008954:Models, Biological; D012038:Regeneration / Q000502:physiology; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*