Mathematical models for CFSE labelled lymphocyte dynamics: asymmetry and time-lag in division
Abstract
Since their invention in 1994, fluorescent dyes such as carboxyfluorescein diacetate succinimidyl ester (CFSE) are used for cell proliferation analysis in flow cytometry. Importantly, the interpretation of such assays relies on the assumption that the label is divided equally between the daughter cells upon cell division. However, recent experimental studies indicate that division of cells is not perfectly symmetric and there is unequal distribution of protein between sister cell pairs. The uneven partition of protein or mass to daughter cells can lead to an overlap in the generations of CFSE-labelled cells with straightforward consequences for the resolution of individual generations. Numerous mathematical models developed so far for the analysis of CFSE proliferation assay incorporate the premise that the CFSE fluorescence intensity is halved in the two daughter cells. Here, we propose a novel modelling approach for the analysis of the CFSE cell proliferation assays which are characterized by poorly resolved peaks of cell generations in flow cytometric histograms. We formulate a mathematical model in the form of a system of delay hyperbolic partial differential equations which provides a good agreement with the CFSE histogram...Continue Reading
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