Quantifying cell turnover using CFSE data

Quantifying cell turnover using CFSE data
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DOI:
10.1016/j.jim.2005.01.011
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发表时间:
2005-03-01
影响因子:
2.2
通讯作者:
Antia, R
Antia, R
中科院分区:
医学4区
文献类型:
--
作者:
Ganusov, VV;Pilyugin, SS;Antia, R

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CFSE染料稀释测定广泛用于测定给定CFSE标记的细胞在体外和体内经历的分裂次数。在本文中,我们考虑如何使用CFSE(CFSE数据)获得的数据可以用来估计参数决定细胞分裂和死亡。对于同质细胞群体(即,细胞分裂和死亡的参数与时间和细胞分裂次数无关的群体),我们考虑了一个特定的基于生物学的“Smith-Martin”细胞周转模型,并分析了三种不同的估计其参数的技术:直接拟合,间接拟合和重新密封方法。我们发现,仅使用CFSE数据,分裂阶段的持续时间(即,大约细胞周期的S+G(2)+M期)可以使用任一技术来估计。在某些情况下,平均分裂或细胞周期时间可以使用模型解与数据的直接拟合或通过使用Gett-Hodgkin方法[Gett A.和Hodgkin,P.2000。T细胞信号整合的细胞演算。1:239-244]。在承诺分裂期间的死亡率估计(即,在细胞周期的G1期附近)和在分裂期期间,仅使用CFSE数据可能不可行。我们建议,测量一个额外的参数,细胞分裂的分数,可以允许估计所有的模型参数,包括在细胞周期的不同阶段的死亡率。(c)2005 Elsevier B. V.保留所有权利。
The CFSE dye dilution assay is widely used to determine the number of divisions a given CFSE labelled cell has undergone in vitro and in vivo. In this paper, we consider how the data obtained with the use of CFSE (CFSE data) can be used to estimate the parameters determining cell division and death. For a homogeneous cell population (i.e., a population with the parameters for cell division and death being independent of time and the number of divisions cells have undergone), we consider a specific biologically based "Smith-Martin" model of cell turnover and analyze three different techniques for estimation of its parameters: direct fitting, indirect fitting and resealing method. We find that using only CFSE data, the duration of the division phase (i.e., approximately the S+G(2)+M phase of the cell cycle) can be estimated with the use of either technique. In some cases, the average division or cell cycle time can be estimated using the direct fitting of the model solution to the data or by using the Gett-Hodgkin method [Gett A. and Hodgkin, P. 2000. A cellular calculus for signal integration by T cells. Nat. Immunol. 1:239-244]. Estimation of the death rates during commitment to division (i.e., approximately the G, phase of the cell cycle) and during the division phase may not be feasible with the use of only CFSE data. We propose that measuring an additional parameter, the fraction of cells in division, may allow estimation of all model parameters including the death rates during different stages of the cell cycle. (c) 2005 Elsevier B.V. All rights reserved.