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Quantifying cell cycle regulation by tissue crowding
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DOI：10.1016/j.bpj.2024.05.003.png)
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The spatiotemporal coordination and regulation of cell proliferation is fundamental in many aspects of development and tissue maintenance. Cells have the ability to adapt their division rates in response to mechanical constraints, yet we do not fully understand how cell proliferation regulation impacts cell migration phenomena. Here, we present a minimal continuum model of cell migration with cell cycle dynamics, which includes density-dependent effects and hence can account for cell proliferation regulation. By combining minimal mathematical modeling, Bayesian inference, and recent experimental data, we quantify the impact of tissue crowding across different cell cycle stages in epithelial tissue expansion experiments. Our model suggests that cells sense local density and adapt cell cycle progression in response, during G1 and the combined S/G2/M phases, providing an explicit relationship between each cell-cycle-stage duration and local tissue density, which is consistent with several experimental observations. Finally, we compare our mathematical model's predictions to different experiments studying cell cycle regulation and present a quantitative analysis on the impact of density-dependent regulation on cell migration patterns. Our work presents a systematic approach for investigating and analyzing cell cycle data, providing mechanistic insights into how individual cells regulate proliferation, based on population-based experimental measurements. SIGNIFICANCE The correct regulation of cell proliferation is crucial for the emergence of collective cell behavior during tissue morphogenesis, homeostasis, and regeneration. Moreover, uncontrolled cell division often leads to tumor formation. Here, we propose a mathematical model of cell migration with cell cycle dynamics that accounts for density-dependent effects regulating cell cycle progression. Our model is capable of describing the spatiotemporal cell cycle dynamics observed during epithelial tissue expansion. By combining experimental data, Bayesian inference, and minimal modeling, we describe how each cell cycle phase depends on local cell density, and we quantify the impact of tissue crowding on cell proliferation patterns.
Keyword:
PARAMETER IDENTIFIABILITY
CONTACT INHIBITION
SCRATCH ASSAYS
PROLIFERATION
MODELS
INDICATORS
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期刊
IF:
3.1
论文数:
5.0W
被引数:
4.4W
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