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July 1st, 2025
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Lund University
cancer biology
biorxiv

Inferring cell dynamics in stress-induced neuroblastoma cell cultures

Hafiichuk, K.Open in Google Scholar•Hamis, S.Open in Google Scholar•Karlsson, J.Open in Google Scholar•Gisselsson, D.Open in Google Scholar•Chattopadhyay, S.Open in Google Scholar

Neuroblastoma is characterised by significant intratumoural heterogeneity which complicates treatments. Phenotypic plasticity, i.e., the ability of cells to alter their phenotype without genetic mutations, is a key factor contributing to this heterogeneity. In this study, we quantify cell actions and cell-to-cell interactions that lead to phenotypic adaptation in vitro under stress, specifically low-nutrient conditions. We initially record dynamic cell counts under various nutrient conditions for two neuroblastoma cell lines with known phenotype differences. Subsequently, we compile a list of plausible biological processes that could transpire within the aforementioned systems. We then construct candidate models employing mass-action kinetics. To quantitatively infer processes that lead to phenotypic adaptation, we perform a model selection based on computational Bayesian inference methods.Our results suggest that cell-to-cell interactions promote phenotypic adaptation and that the rate of this adaptation increases with decreasing nutrient concentrations. We perform flow cytometry-based experiments to corroborate changes in phenotype composition in response to both nutrient-deprived and treatmentinduced stress conditions.

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