Department of Biostatistics & Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Biol Direct. 2010 Jun 22;5:41. doi: 10.1186/1745-6150-5-41.
Over the past decade, flow cytometric CFSE-labeling experiments have gained considerable popularity among experimentalists, especially immunologists and hematologists, for studying the processes of cell proliferation and cell death. Several mathematical models have been presented in the literature to describe cell kinetics during these experiments.
We propose a multi-type age-dependent branching process to model the temporal development of populations of cells subject to division and death during CFSE-labeling experiments. We discuss practical implementation of the proposed model; we investigate a competing risk version of the process; and we identify the classes of cellular dependencies that may influence the expectation of the process and those that do not. An application is presented where we study the proliferation of human CD8+ T lymphocytes using our model and a competing risk branching process.
The proposed model offers a widely applicable approach to the analysis of CFSE-labeling experiments. The model fitted very well our experimental data. It provided reasonable estimates of cell kinetics parameters as well as meaningful insights into the processes of cell division and cell death. In contrast, the competing risk branching process could not describe the kinetics of CD8+ T cells. This suggested that the decision of cell division or cell death may be made early in the cell cycle if not in preceding generations. Also, we show that analyses based on the proposed model are robust with respect to cross-sectional dependencies and to dependencies between fates of linearly filiated cells.
This article was reviewed by Marek Kimmel, Wai-Yuan Tan and Peter Olofsson.
在过去的十年中，流式细胞术 CFSE 标记实验在实验学家中，尤其是免疫学家和血液学家中变得非常流行，用于研究细胞增殖和细胞死亡的过程。文献中已经提出了几种数学模型来描述这些实验过程中的细胞动力学。
我们提出了一种多类型与年龄相关的分支过程模型，用于模拟 CFSE 标记实验中分裂和死亡过程中细胞群体的时间发展。我们讨论了所提出模型的实际实现；我们研究了过程的竞争风险版本；并确定了可能影响过程期望的和不影响过程期望的细胞依赖性类别。应用实例中，我们使用我们的模型和竞争风险分支过程来研究人 CD8+T 淋巴细胞的增殖。
所提出的模型为 CFSE 标记实验的分析提供了一种广泛适用的方法。该模型非常适合我们的实验数据。它提供了细胞动力学参数的合理估计，以及对细胞分裂和细胞死亡过程的有意义的见解。相比之下，竞争风险分支过程无法描述 CD8+T 细胞的动力学。这表明，如果不是在前几代中，细胞分裂或细胞死亡的决定可能在细胞周期的早期做出。此外，我们表明，基于所提出模型的分析对于截面依赖性和线性谱系细胞命运之间的依赖性是稳健的。
这篇文章由 Marek Kimmel、Wai-Yuan Tan 和 Peter Olofsson 进行了评论。
