Quantifying cellular dynamics in mice using a novel fluorescent division reporter system.

Quantifying cellular dynamics in mice using a novel fluorescent division reporter system.
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使用一种新的荧光分区报告系统对小鼠细胞动力学进行量化。

DOI:
10.3389/fimmu.2023.1157705
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发表时间:
2023
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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--
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细胞群体的动态经常使用脉冲追踪DNA标记技术在体内研究。当与数学模型相结合时,感兴趣的群体内的标记摄取和损失的动力学允许人们通过死亡或向前分化来估计细胞产生和周转的速率。在这里,我们探索一种替代的方法,定量细胞动力学,使用细胞命运映射小鼠模型,其中分裂细胞可以诱导组成型表达荧光蛋白,使用Ki67报告构建体。我们使用脉冲追踪的方法与这种报告小鼠系统来测量使用各种建模方法的幼稚CD4和CD8 T细胞的寿命和分裂率,并表明它们都与来自其他已发表的方法的估计值一致。然而,我们建议,要获得无偏的参数估计和充分的措施,他们的不确定性之一,应同时建模的时间过程中的标记细胞的频率在两个人口的利益和它的前体。我们的结论是,Ki67报告小鼠提供了一个有前途的系统建模细胞动力学。
The dynamics of cell populations are frequently studied in vivo 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.
胸腺和最近的胸腺移民在维持成年外周淋巴细胞库中的作用。
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