黑色素瘤 MITF 变阻器的新兴种群动力学定量模型
A quantitative model for the emergent population dynamics of the melanoma MITF rheostat
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中文总结 AI 辅助
研究黑色素瘤种群动态，构建多尺度表型结构偏微分方程模型，揭示三种长期种群行为，强调单细胞表型可逆性与种群尺度不同，为理解黑色素瘤种群动态和细胞可塑性提供新认知。
中文摘要 AI 辅助
癌症进展由具有相同驱动突变的细胞采用生物学上不同的适应性表型的能力驱动。然而，肿瘤内表型异质性所隐含的种群动态却知之甚少。黑色素瘤是一种高度侵袭性的皮肤癌，是探索表型转换的极佳模型，部分原因是表型特征由黑素细胞相关转录因子（MITF）活性赋予。在此，我们开发并分析了一个多尺度表型结构的偏微分方程模型，用于表皮中的黑色素瘤细胞群体，从亚细胞 MITF 动态发展到充分混合和径向解析的种群模型。数值解表明该模型允许三种不同且稳定的长期种群行为：一种由增殖细胞和无侵袭潜力的非循环、分化细胞组成的缓慢生长的黑色素瘤；一种具有侵袭核心的快速传播的黑色素瘤；以及一种具有振荡核心动态的快速生长的黑色素瘤。更广泛地说，分析还强调单个细胞的表型可逆性并不意味着种群尺度上表型分布的可逆性。因此，单细胞水平的特性（如侵袭能力的可逆性）必须谨慎地外推到具有耦合细胞动态的种群。这些发现进一步加深了对黑色素瘤种群动态和细胞可塑性的理解。
英文摘要
Cancer progression is driven by the ability of cells with identical driver mutations to adopt biologically distinct adaptive phenotypes. Yet the population dynamics implied by intratumour phenotypic heterogeneity is poorly understood. Melanoma is an excellent setting to study phenotype switching, in part because phenotypic identity is conferred by melanocyte inducing transcription factor (MITF) activity. Here we develop a multiscale phenotype-structured partial differential equation model for epidermal melanoma cell populations, first considering subcellular MITF and then spatially uniform and spatially heterogeneous populations. The model admits three stable long-term behaviours: slow growth with proliferative cells and non-cycling differentiated cells; faster expansion, with an invasive core; and rapid growth with oscillatory core dynamics. More broadly, the analysis highlights that phenotype reversibility by individual cells does not imply reversibility of phenotype population distributions. Hence, single-cell properties (e.g., reversibility of invasive capacity) must be extrapolated with caution to populations with coupled cell dynamics.
