Department of Computer Science, University of Sheffield, Sheffield, United Kingdom.
Sci Rep. 2013;3:1904. doi: 10.1038/srep01904.
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.
皮肤中的上皮细胞更新是通过角质形成细胞的不断更替和分化来实现的。目前有三种流行的假说可以解释基底角质形成细胞的再生和表皮的动态平衡：1）不对称分裂（干细胞-过渡扩增细胞）；2）群体不对称性（具有随机命运的祖细胞）；3）具有干细胞的群体不对称性。在这项研究中，我们使用这些假说，结合表皮的三维基于主体的模型来研究谱系动力学。该模型模拟了三年的表皮生长和维持。追踪了每个增殖细胞的后代。虽然所有谱系都在不对称分裂中保留下来，但当假设群体不对称时，绝大多数都丢失了。第三个假说是通过在静止的干细胞中保留遗传异质性，以及内在的皮肤老化和遗传突变积累机制，为自我更新提供了最可靠的机制。
