Stretched cell cycle model for proliferating lymphocytes
Stretched cell cycle model for proliferating lymphocytes
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DOI：
10.1073/pnas.1322420111
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发表时间：
2014-04-29
影响因子：
11.1
通讯作者：
Hodgkin, Philip D.
中科院分区：
文献类型：
--
作者：
Dowling, Mark R.;Kan, Andrey;Hodgkin, Philip D.
细胞周期时间的随机变化是生长群体中其他相似细胞的一致特征。经典研究得出结论，大部分变化发生在G（1）阶段，许多数学模型假设穿越S/G2/M阶段的时间恒定。通过直接观察报告S期开始的转基因荧光融合蛋白，我们确定分裂的B和T淋巴细胞在S/G2/M期花费的总分裂时间的比例接近固定，并且该比例在同胞细胞之间相关。这一结果与假设连续阶段的独立时间的模型不一致。相反，我们提出了一个拉伸模型分裂淋巴细胞的细胞周期的所有部分是成比例的总分裂时间。基于拉伸细胞周期模型的数据拟合可以显着改善从用于监测免疫细胞动力学的DNA标记数据中提取的细胞周期参数的估计。
Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G(1) phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G2/M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics.