Data from: Sources of variability in cytosolic calcium transients triggered by stimulation of homogeneous uro-epithelial cell monolayers

Epithelial tissue structure is the emergent outcome of the interactions between large numbers of individual cells. Experimental cell biology offers an important tool to unravel these complex interactions, but current methods of analysis tend to be limited to mean field approaches or representation by selected subsets of cells. This may result in bias towards cells that respond in a particular way and/or neglect local, context-specific cell responses. Here, an automated algorithm was applied to examine in detail the individual calcium transients evoked in genetically homogeneous, but asynchronous populations of cultured non-immortalized normal human urothelial cells when subjected to either the global application of an external agonist or a localized scratch wound. The recorded calcium transients were classified automatically according to a set of defined metrics and distinct sub-populations of cells that responded in qualitatively different ways were observed. The nature of this variability in the homogeneous cell population was apportioned to two sources: intrinsic variation in individual cell responses and extrinsic variability due to context-specific factors of the environment, such as spatial heterogeneity. Statistically significant variation in the features of the calcium transients evoked by scratch wounding according to proximity to the wound edge was identified. The manifestation of distinct sub-populations of cells is considered central to the coordination of population-level response resulting in wound closure.

上皮组织（epithelial tissue）的结构是大量单个细胞相互作用所产生的涌现性结果。实验细胞生物学为解析这类复杂的细胞互作提供了关键工具，但当前的分析方法往往局限于平均场（mean field）方法，或是仅通过筛选得到的细胞亚群来表征整体系统。这类分析策略可能会导致对特定响应模式细胞的偏向性选取，同时忽略局部、依赖环境背景的细胞响应。本研究采用自动化算法，详细考察了基因均一但异步生长的培养未永生化正常人类尿道上皮（urothelial）细胞群，在分别接受外源激动剂全局给药或局部划痕损伤时所诱发的单个钙瞬变（calcium transient）。研究人员通过一系列预设的量化指标，对记录到的钙瞬变进行自动分类，进而观察到了响应模式存在质的差异的不同细胞亚群。这种基因均一细胞群内的响应异质性，可归因于两类来源：单个细胞响应的内在变异，以及由环境背景特异性因素（如空间异质性（spatial heterogeneity））所导致的外在变异。研究还发现，划痕损伤诱发的钙瞬变特征，会根据细胞与伤口边缘的距离呈现出具有统计学显著性的差异。学界普遍认为，不同细胞亚群的存在，是协调群体层面响应以实现伤口闭合的核心机制。