Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States.
Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2023 Jul 27;14:1157705. doi: 10.3389/fimmu.2023.1157705. eCollection 2023.
The dynamics of cell populations are frequently studied using pulse-chase DNA labeling techniques. When combined with mathematical models, the kinetic of label uptake and loss within a population of interest then allows one to estimate rates of cell production and turnover through death or onward differentiation. Here we explore an alternative method of quantifying cellular dynamics, using a cell fate-mapping mouse model in which dividing cells can be induced to constitutively express a fluorescent protein, using a Ki67 reporter construct. We use a pulse-chase approach with this reporter mouse system to measure the lifespans and division rates of naive CD4 and CD8 T cells using a variety of modeling approaches, and show that they are all consistent with estimates derived from other published methods. However we propose that to obtain unbiased parameter estimates and full measures of their uncertainty one should simultaneously model the timecourses of the frequencies of labeled cells within both the population of interest and its precursor. We conclude that Ki67 reporter mice provide a promising system for modeling cellular dynamics.
细胞群体的动力学通常使用脉冲追踪 DNA 标记技术进行研究。当与数学模型结合使用时，感兴趣的群体中标记摄取和损失的动力学可以通过细胞的产生和通过死亡或继续分化的损失来估计周转率。在这里，我们探索了一种量化细胞动力学的替代方法，使用一种细胞命运图谱小鼠模型，其中可以使用 Ki67 报告基因构建体诱导分裂细胞持续表达荧光蛋白。我们使用该报告基因小鼠系统进行脉冲追踪方法，使用各种建模方法来测量幼稚 CD4 和 CD8 T 细胞的寿命和分裂率，并表明它们都与从其他已发表方法得出的估计值一致。但是，我们提出为了获得无偏的参数估计值并充分衡量其不确定性，应该同时对感兴趣的群体及其前体中标记细胞的频率的时程进行建模。我们得出结论，Ki67 报告基因小鼠为建模细胞动力学提供了一个有前途的系统。
