How are estimated cellular turnover rates influenced by the dynamics of a source population?
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1013052 |
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| author | Arpit C Swain José A M Borghans Rob J de Boer |
| author_facet | Arpit C Swain José A M Borghans Rob J de Boer |
| author_sort | Arpit C Swain |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5e6da2ce97ef46f1934af5a564807977 |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-5e6da2ce97ef46f1934af5a5648079772025-08-20T03:25:19ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-05-01215e101305210.1371/journal.pcbi.1013052How are estimated cellular turnover rates influenced by the dynamics of a source population?Arpit C SwainJosé A M BorghansRob J de BoerEstimating 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.https://doi.org/10.1371/journal.pcbi.1013052 |
| spellingShingle | Arpit C Swain José A M Borghans Rob J de Boer How are estimated cellular turnover rates influenced by the dynamics of a source population? PLoS Computational Biology |
| title | How are estimated cellular turnover rates influenced by the dynamics of a source population? |
| title_full | How are estimated cellular turnover rates influenced by the dynamics of a source population? |
| title_fullStr | How are estimated cellular turnover rates influenced by the dynamics of a source population? |
| title_full_unstemmed | How are estimated cellular turnover rates influenced by the dynamics of a source population? |
| title_short | How are estimated cellular turnover rates influenced by the dynamics of a source population? |
| title_sort | how are estimated cellular turnover rates influenced by the dynamics of a source population |
| url | https://doi.org/10.1371/journal.pcbi.1013052 |
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