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How are estimated cellular turnover rates influenced by the dynamics of a source population?

Fig 2

The rate of label gain in the POI is also lower than the POI’s true turnover rate,

, if the precursors turn over more slowly than the POI. The filled circles mark the timepoints at which the slopes were calculated (note that unlike and , is constant over time). A small offset was added to the slopes for better visualization. The slopes denoting the initial label gain rate, (equation 9c), and the final label gain rate, (equation 9e), of the POI were given a small negative offset, while those denoting the true turnover rate, , and the initial label loss rate, (equation 11d), of the POI were given a small positive offset. The slopes were calculated as the label gain or loss rate multiplied by the total, i.e., one, or the fraction of labelled cells (i.e., ), respectively, for example, . The loss rate of the precursors, , and the POI, , were set to 0.2 and 0.5, respectively. The division rate of the POI, , was either set to 0.25 (in (a) and (c)) or to 0 (in (b) and (d)). Note that the dynamics in (a) and (d) are identical, which can also be seen in Table 1 (see the sub-section Division-linked differentiation below for details). In these simulations, the body deuterium concentration was described as a step function (equation 1e). Note the large difference in the labelling curves of a non-dividing POI depending on whether differentiation is accompanied by cell division (panels (b) and (d)).

doi: https://doi.org/10.1371/journal.pcbi.1013052.g002