An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition - Archive ouverte HAL Access content directly
Preprints, Working Papers, ... Year : 2023

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 how different possible processes interplay in shaping the dynamics of E-M heterogeneity: a) intracellular regulatory interaction among biomolecules, b) cell division and death, and c) stochastic cell-state transition (biochemical reaction noise and asymmetric cell division). Here, we propose a Cell Population Balance (Partial Differential Equation (PDE)) based model that captures the dynamics of cell population density along the E-M phenotypic axis due to abovementioned multi-scale cellular processes. We demonstrate how population distribution resulting from intracellular regulatory networks driving cell-state transition gets impacted by stochastic fluctuations in E-M regulatory biomolecules, differences in growth rates among cell subpopulations, and initial population distribution. Further, we reveal that a linear dependence of the cell growth rate on the population heterogeneity is sufficient to recapitulate the faster in vivo growth of orthotopic injected heterogeneous E-M subclones reported before experimentally. Overall, our model contributes to the combined understanding of intracellular and cell-population levels dynamics in the emergence of E-M heterogeneity in a cell population.
Fichier principal
Vignette du fichier
main.pdf (7.53 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-04208893 , version 1 (15-09-2023)

Identifiers

  • HAL Id : hal-04208893 , version 1

Cite

Jules Guilberteau, Paras Jain, Mohit Kumar Jolly, Camille Pouchol, Nastassia Pouradier Duteil. An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition. 2023. ⟨hal-04208893⟩
6 View
1 Download

Share

Gmail Facebook X LinkedIn More