Seaman Laura, Meixner Walter, Snyder John, Rajapakse Indika
a Department of Computational Medicine and Bioinformatics ; University of Michigan ; Ann Arbor , MI USA.
b Microsoft Research ; Redmond , WA USA.
Nucleus. 2015;6(5):408-16. doi: 10.1080/19491034.2015.1095432.
Morphology of the cell nucleus has been used as a key indicator of disease state and prognosis, but typically without quantitative rigor. It is also not well understood how nuclear morphology varies with time across different genetic backgrounds in healthy cells. To help answer these questions we measured the size and shape of nuclei in cell-cycle-synchronized primary human fibroblasts from 6 different individuals at 32 time points over a 75 hour period.
The nucleus was modeled as an ellipsoid and its dynamics analyzed. Shape and volume changed significantly over this time. Two prominent frequencies were found in the 6 individuals: a 17 hour period consistent with the cell cycle and a 26 hour period. Our findings suggest that the shape of the nucleus changes over time and thus any time-invariant shape property may provide a misleading characterization of cellular populations at different phases of the cell cycle. The proposed methodology provides a general method to analyze morphological change using multiple time points even for non-live-cell experiments.
细胞核形态已被用作疾病状态和预后的关键指标，但通常缺乏定量的严谨性。目前对于健康细胞中不同遗传背景下细胞核形态如何随时间变化也尚未完全了解。为了帮助回答这些问题，我们在75小时内的32个时间点测量了来自6个不同个体的细胞周期同步化的原代人成纤维细胞核的大小和形状。
将细胞核建模为椭球体并分析其动态变化。在此期间，形状和体积发生了显著变化。在这6个个体中发现了两个显著的频率：一个与细胞周期一致的17小时周期和一个26小时周期。我们的研究结果表明，细胞核的形状会随时间变化，因此任何不随时间变化的形状特性可能会对细胞周期不同阶段的细胞群体特征给出误导性描述。所提出的方法提供了一种通用方法，即使对于非活细胞实验，也能使用多个时间点来分析形态变化。
