Mathematical modeling and quantitative analysis of phenotypic plasticity during tumor evolution based on single-cell data.
Mathematical model
Phenotypic heterogeneity and plasticity
Quantitative analysis
Tumor malignancy
Wave speed
Journal
Journal of mathematical biology
ISSN: 1432-1416
Titre abrégé: J Math Biol
Pays: Germany
ID NLM: 7502105
Informations de publication
Date de publication:
20 Aug 2024
20 Aug 2024
Historique:
received:
11
02
2024
accepted:
08
08
2024
revised:
24
06
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
20
8
2024
Statut:
epublish
Résumé
Tumor is a complex and aggressive type of disease that poses significant health challenges. Understanding the cellular mechanisms underlying its progression is crucial for developing effective treatments. In this study, we develop a novel mathematical framework to investigate the role of cellular plasticity and heterogeneity in tumor progression. By leveraging temporal single-cell data, we propose a reaction-convection-diffusion model that effectively captures the spatiotemporal dynamics of tumor cells and macrophages within the tumor microenvironment. Through theoretical analysis, we obtain the estimate of the pulse wave speed and analyze the stability of the homogeneous steady state solutions. Notably, we employe the AddModuleScore function to quantify cellular plasticity. One of the highlights of our approach is the introduction of pulse wave speed as a quantitative measure to precisely gauge the rate of cell phenotype transitions, as well as the novel implementation of the high-plasticity cell state/low-plasticity cell state ratio as an indicator of tumor malignancy. Furthermore, the bifurcation analysis reveals the complex dynamics of tumor cell populations. Our extensive analysis demonstrates that an increased rate of phenotype transition is associated with heightened malignancy, attributable to the tumor's ability to explore a wider phenotypic space. The study also investigates how the proliferation rate and the death rate of tumor cells, phenotypic convection velocity, and the midpoint of the phenotype transition stage affect the speed of tumor cell phenotype transitions and the progression to adenocarcinoma. These insights and quantitative measures can help guide the development of targeted therapeutic strategies to regulate cellular plasticity and control tumor progression effectively.
Identifiants
pubmed: 39162836
doi: 10.1007/s00285-024-02133-5
pii: 10.1007/s00285-024-02133-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
34Subventions
Organisme : Major Research Plan of the National Natural Science Foundation of China
ID : No.92374108
Organisme : Key Program of the National Nature Science Foundation of China
ID : No. 12331018 and No. 11831015
Organisme : Key Program of the National Nature Science Foundation of China
ID : No. 11831015
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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