Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
J R Soc Interface. 2022 Feb;19(187):20210784. doi: 10.1098/rsif.2021.0784. Epub 2022 Feb 23.
It has been hypothesized that the structure of tissues and the hierarchy of differentiation from stem cell to terminally differentiated cell play a significant role in reducing the incidence of cancer in that tissue. One specific mechanism by which this risk can be reduced is by minimizing the number of divisions-and hence the mutational risk-that cells accumulate as they divide to maintain tissue homeostasis. Here, we investigate a mathematical model of cell division in a hierarchical tissue, calculating and minimizing the divisional load while constraining parameters such that homeostasis is maintained. We show that the minimal divisional load is achieved by binary division trees with progenitor cells incapable of self-renewal. Contrary to the protection hypothesis, we find that an increased stem cell turnover can lead to lower divisional load. Furthermore, we find that the optimal tissue structure depends on the time horizon of the duration of homeostasis, with faster stem cell division favoured in short-lived organisms and more progenitor compartments favoured in longer-lived organisms.
人们推测，组织的结构和从干细胞到终末分化细胞的分化层次在降低组织中癌症的发生率方面起着重要作用。可以通过减少细胞分裂的次数（从而减少突变风险）来降低这种风险，因为细胞在分裂以维持组织内稳态时会发生分裂。在这里，我们研究了一个层次组织中细胞分裂的数学模型，在维持内稳态的同时计算并最小化分裂负荷，同时约束参数。我们发现，通过不能自我更新的祖细胞的二叉分裂树可以实现最小的分裂负荷。与保护假说相反，我们发现增加干细胞的更替可以降低分裂负荷。此外，我们发现最佳的组织结构取决于内稳态持续时间的时间范围，在寿命较短的生物体中，较快的干细胞分裂更为有利，而在寿命较长的生物体中，则更为有利。
