期刊
JOURNAL OF THE ROYAL SOCIETY INTERFACE
卷 19, 期 187, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsif.2021.0784
关键词
tissue structure; differentiation; somatic mutation; cancer; haematopoiesis; optimization
资金
- Swiss National Science Foundation [310030B_176401]
- Swiss National Science Foundation (SNF) [310030B_176401] Funding Source: Swiss National Science Foundation (SNF)
The divisional load of cells and the hierarchical structure of tissue have significant impact on reducing cancer incidence. It is found that minimizing the number of cell divisions and increasing stem cell turnover can decrease mutational risk and divisional load.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据