An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition
Abstract Phenotypic heterogeneity along the epithelial-mesenchymal (E-M) axis contributes to cancer metastasis and drug resistance. Recent experimental efforts have collated detailed time-course data on the emergence and dynamics of E-M heterogeneity in a cell population. However, it remains unclear...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-025-00502-4 |
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| Summary: | Abstract Phenotypic heterogeneity along the epithelial-mesenchymal (E-M) axis contributes to cancer metastasis and drug resistance. Recent experimental efforts have collated detailed time-course data on the emergence and dynamics of E-M heterogeneity in a cell population. However, it remains unclear how different intra- and inter-cellular processes shape the dynamics of E-M heterogeneity. Here, using Cell Population Balance model, we capture the dynamics of cell density along E-M phenotypic axis resulting from interplay between—(a) intracellular regulatory interaction among biomolecules, (b) cell division and death and (c) stochastic cell-state transition. We find that while the existence of E-M heterogeneity depends on intracellular regulation, heterogeneity gets enhanced with stochastic cell-state transitions and diminished by growth rate differences. Further, resource competition among E-M cells can lead to both bi-phasic growth of the total population and/or bi-stability in the phenotypic composition. Overall, our model highlights complex interplay between cellular processes shaping dynamic patterns of E-M heterogeneity. |
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| ISSN: | 2056-7189 |