论文标题
调节干细胞动力学通过排除量
Regulation of stem cell dynamics through volume exclusion
论文作者
论文摘要
成人组织的维持和再生依赖于干细胞的自我更新。没有过度增殖的再生需要精确调节干细胞增殖和分化速率。尚不完全了解不同组织中这种调节机制的性质,以及如何将它们纳入干细胞种群动态模型中。关键的出生死亡(CBD)过程被广泛用于模拟干细胞种群,以捕获关键现象,例如克隆大小分布中的缩放定律。但是,CBD过程忽略了监管机制。在这里,我们提出了使用体积排除(VBD)的出生死亡过程,该过程是考虑拥挤效应的出生死亡过程的变化,例如由于干细胞生态裂的空间有限而引起的。尽管确定速率方程式预测了单个非平凡的吸引稳态,但主方程可预测干细胞数的灭绝和瞬态分布,具有三种可能的行为:长期寿命的准稳态状态和短暂的双峰或单峰分布。在所有情况下,我们都使用重量化的系统大小扩展,准稳态状态近似和WKB方法将解决方案近似于VBD主方程。我们的研究表明,干细胞种群的尺寸分布带有标志,这些标志可用于检测通过排除量的负面反馈。
Maintenance and regeneration of adult tissues rely on the self-renewal of stem cells. Regeneration without over-proliferation requires precise regulation of the stem cell proliferation and differentiation rates. The nature of such regulatory mechanisms in different tissues, and how to incorporate them in models of stem cell population dynamics, is incompletely understood. The critical birth-death (CBD) process is widely used to model stem cell populations, capturing key phenomena, such as scaling laws in clone size distributions. However, the CBD process neglects regulatory mechanisms. Here, we propose the birth-death process with volume exclusion (vBD), a variation of the birth-death process that considers crowding effects, such as may arise due to limited space in a stem cell niche. While the deterministic rate equations predict a single non-trivial attracting steady state, the master equation predicts extinction and transient distributions of stem cell numbers with three possible behaviours: long-lived quasi-steady state, and short-lived bimodal or unimodal distributions. In all cases, we approximate solutions to the vBD master equation using a renormalised system-size expansion, quasi-steady state approximation and the WKB method. Our study suggests that the size distribution of a stem cell population bears signatures that are useful to detect negative feedback mediated via volume exclusion.