Savill Nicholas J
Centre for Theoretical Modelling in Medicine, Department of Mathematics, Heriot-Watt University, Edinburgh, UK.
Cell Prolif. 2003 Feb;36(1):1-26. doi: 10.1046/j.1365-2184.2003.00257.x.
There are three categories of keratinocytes in the germinative compartment of the epidermis - stem, transit-amplifying and post-mitotic. Their population structure is hierarchical. This means that stem cells differentiate into transit-amplifying cells which, after a few rounds of division, become post-mitotic cells. The cell processes of birth, differentiation, death and migration affect the composition and proliferation rate of the germinative compartment. These phenomena are quantified by various cell kinetic parameters. In this paper we derive equations that relate these parameters for different models of hierarchically structured cell populations in equilibrium. We include in the models asymmetric and symmetric division, variations in cell-cycle times, apoptosis and variation in the number of transit generations. We conclude that variation in cell-cycle times need only be considered if apoptosis is not negligible. If it is negligible, then only average cell-cycle times are needed. Unfortunately, it is impossible to predict the importance of apoptosis from the available experimental data. However, the strength of its effect is determined by the other parameters, especially the fraction of cycling stem cells. We show that variation in the number of transit generations can have a potentially large effect on cell birth rate. We also show that cell birth rate does not directly depend on the mean transit-amplifying cell-cycle time, only on the mean stem cell-cycle time. We argue that 'homogeneous cell population' equations should not be used to study hierarchical cell populations as has been done in the past. Finally we argue that stem cell parameters and transit-amplifying cell parameters should not be lumped together.
在表皮生发层中有三类角质形成细胞——干细胞、过渡扩增细胞和有丝分裂后细胞。它们的群体结构呈层级状。这意味着干细胞分化为过渡扩增细胞，过渡扩增细胞经过几轮分裂后成为有丝分裂后细胞。细胞的产生、分化、死亡和迁移过程会影响生发层的组成和增殖率。这些现象通过各种细胞动力学参数进行量化。在本文中，我们推导了平衡状态下分层结构细胞群体不同模型中这些参数之间的关系式。我们在模型中纳入了不对称和对称分裂、细胞周期时间的变化、细胞凋亡以及过渡世代数的变化。我们得出结论：只有当细胞凋亡不可忽略时，才需要考虑细胞周期时间的变化。如果细胞凋亡可忽略不计，那么只需要平均细胞周期时间。不幸的是，根据现有的实验数据无法预测细胞凋亡的重要性。然而，其影响强度由其他参数决定，尤其是循环干细胞的比例。我们表明，过渡世代数的变化可能对细胞产生率有潜在的重大影响。我们还表明，细胞产生率并不直接取决于过渡扩增细胞的平均细胞周期时间，仅取决于干细胞的平均细胞周期时间。我们认为，不应像过去那样使用“均匀细胞群体”方程来研究分层细胞群体。最后，我们认为不应将干细胞参数和过渡扩增细胞参数混为一谈。
