Qiu Yuchi, Chen Weitao, Nie Qing
Department of Mathematics, University of California, Irvine Irvine, CA 92697, USA.
Department of Mathematics, University of California, Riverside Riverside, CA 92507, USA.
Discrete Continuous Dyn Syst Ser B. 2019 Aug;24(8):3971-3994. doi: 10.3934/dcdsb.2018339.
During epithelium tissue maintenance, lineages of cells differentiate and proliferate in a coordinated way to provide the desirable size and spatial organization of different types of cells. While mathematical models through deterministic description have been used to dissect role of feedback regulations on tissue layer size and stratification, how the stochastic effects influence tissue maintenance remains largely unknown. Here we present a stochastic continuum model for cell lineages to investigate how both layer thickness and layer stratification are affected by noise. We find that the cell-intrinsic noise often causes reduction and oscillation of layer size whereas the cell-extrinsic noise increases the thickness, and sometimes, leads to uncontrollable growth of the tissue layer. The layer stratification usually deteriorates as the noise level increases in the cell lineage systems. Interestingly, the morphogen noise, which mixes both cell-intrinsic noise and cell-extrinsic noise, can lead to larger size of layer with little impact on the layer stratification. By investigating different combinations of the three types of noise, we find the layer thickness variability is reduced when cell-extrinsic noise level is high or morphogen noise level is low. Interestingly, there exists a tradeoff between low thickness variability and strong layer stratification due to competition among the three types of noise, suggesting robust layer homeostasis requires balanced levels of different types of noise in the cell lineage systems.
在上皮组织维持过程中，细胞谱系以协调的方式分化和增殖，以提供不同类型细胞所需的大小和空间组织。虽然通过确定性描述的数学模型已被用于剖析反馈调节对组织层大小和分层的作用，但随机效应如何影响组织维持在很大程度上仍不清楚。在这里，我们提出了一个细胞谱系的随机连续模型，以研究层厚度和层分层如何受到噪声的影响。我们发现，细胞内在噪声通常会导致层大小的减小和振荡，而细胞外在噪声会增加厚度，有时还会导致组织层的不可控生长。在细胞谱系系统中，随着噪声水平的增加，层分层通常会恶化。有趣的是，混合了细胞内在噪声和细胞外在噪声的形态发生素噪声可以导致更大的层大小，而对层分层影响很小。通过研究三种类型噪声的不同组合，我们发现当细胞外在噪声水平高或形态发生素噪声水平低时，层厚度变异性会降低。有趣的是，由于三种类型噪声之间的竞争，在低厚度变异性和强层分层之间存在权衡，这表明强大的层稳态需要细胞谱系系统中不同类型噪声的平衡水平。
