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Modeling relaxation experiments with a mechanistic model of gene expression
Open accessPublished version of a preprint
Abstract
Background: In the present work, we aimed at modeling a relaxation experiment which consists in selecting a subfraction of a cell population and observing the speed at which the entire initial distribution for a given marker is reconstituted. Methods: For this we first proposed a modification of a previously published mechanistic two-state model of gene expression to which we added a state-dependent proliferation term. This results in a system of two partial differential equations. Under the assumption of a linear dependence of the proliferation rate with respect to the marker level, we could derive the asymptotic profile of the solutions of this model. Results: In order to confront our model with experimental data, we generated a relaxation experiment of the CD34 antigen on the surface of TF1-BA cells, starting either from the highest or the lowest CD34 expression levels. We observed in both cases that after approximately 25 days the distribution of CD34 returns to its initial stationary state. Numerical simulations, based on parameter values estimated from the dataset, have shown that the model solutions closely align with the experimental data from the relaxation experiments. Conclusion: Altogether our results strongly support the notion that cells should be seen and modeled as probabilistic dynamical systems.
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Global quantification of mammalian gene expression control
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“In the case of CD34 + cell relaxation, the linear regression line is given by the slope + ≈ 0.418 , and for CD34 − cells, the slope is − ≈ 0.422 .”
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Metadata
- Authors
- Estavoyer, M., Dufeu, M., Ranson, G., Lefort, S., Voeltzel, T., Maguer-Satta, V., Gandrillon, O., & Lepoutre, T.
- Affiliations
- Lyon 1 Université (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Corresponding author
- Lepoutre, Thomas
- ORCID
- Venue
- BMC Bioinformatics
- Published
- 2024-08-20
- Volume
- 25
- Issue
- 1
- Pages
- 270-270
- ISSN
- 1471-2105 (ISSN-L)
- PMC
- PMC11334594
- OpenAlex
- W4401728618
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Bioinformatics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-21-CE13-004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Physical Sciences › Mathematics › Mathematical Physics › Stochastic processes and statistical mechanics
- Keywords
- gene expression modeling, relaxation experiments, cell proliferation, CD34, partial differential equations, asymptotic profiles, cell population dynamics
- MeSH terms
- Humans, Models, Genetic, Gene Expression, Antigens, CD34, Cell Proliferation
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