Swain Arpit C, Borghans José A M, de Boer Rob J
Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS Comput Biol. 2025 May 12;21(5):e1013052. doi: 10.1371/journal.pcbi.1013052. eCollection 2025 May.
Estimating production and loss rates of cell populations is essential but difficult. The current state-of-the-art method to estimate these rates involves mathematical modelling of deuterium labelling experiments. Current models typically assume that the labelling in the precursors of the population of interest (POI) is proportional to the deuterium enrichment in body water/glucose. This assumption is not always true and it is known that this can have a significant effect on the rates estimated from labelling experiments. Here we quantify the effect that different turnover (replacement) rates of the precursors can have on the estimated proliferation and loss rates of a POI by explicitly modelling the dynamics of the precursors. We first confirm earlier results that the labelling curve of the POI only reflects its own turnover rate if either the turnover rate of the precursors is sufficiently fast, or the contribution from the precursors is sufficiently small. Next, we describe three realistic scenarios with a slowly turning over precursor population, and show how this changes the interpretation of the different parameter estimates. Our analyses underpin that uniquely identifying the turnover rate of a POI requires measurements (or knowledge) on the turnover of its immediate precursors.
估计细胞群体的产生率和损失率至关重要但颇具难度。当前估计这些比率的最先进方法涉及氘标记实验的数学建模。当前模型通常假定目标群体（POI）前体中的标记与体内水/葡萄糖中的氘富集成正比。这一假设并非总是成立，而且已知这会对从标记实验估计出的比率产生重大影响。在此，我们通过明确模拟前体的动态变化，量化前体不同的周转（替换）率对POI估计增殖率和损失率的影响。我们首先证实了早期的结果，即只有在前体的周转率足够快，或者前体的贡献足够小的情况下，POI的标记曲线才仅反映其自身的周转率。接下来，我们描述了三种前体群体周转缓慢的现实情景，并展示了这如何改变对不同参数估计的解释。我们的分析强调，唯一确定POI的周转率需要对其直接前体的周转进行测量（或了解相关信息）。
