Mechanically-driven Stem Cell Separation in Tissues caused by Proliferating Daughter Cells

TL;DR

This paper presents a computational model demonstrating how proliferating daughter cells mechanically influence stem cell distribution in tissues, revealing repulsive interactions that maintain tissue homeostasis and may inform cancer research.

Contribution

The study introduces a novel mechanical model linking cell proliferation to stem cell spatial organization, highlighting emergent repulsive interactions in tissue dynamics.

Findings

Stem cells are spatially isolated due to mechanical repulsion.

The model accurately predicts stem cell distribution in tissues.

Interaction potential decays exponentially with distance.

Abstract

The homeostasis of epithelial tissue relies on a balance between the self-renewal of stem cell populations, cellular differentiation, and loss. Although this balance needs to be tightly regulated to avoid pathologies, such as tumor growth, the regulatory mechanisms, both cell-intrinsic and collective, which ensure tissue steady-state are still poorly understood. Here, we develop a computational model that incorporates basic assumptions of stem cell renewal into distinct populations and mechanical interactions between cells. We find that the model generates unexpected dynamic features: stem cells repel each other in the bulk tissue and are thus found rather isolated, as in a number of in vivo contexts. By mapping the system onto a gas of passive Brownian particles with effective repulsive interactions, that arise from the generated flows of differentiated cells, we show that we can quantitatively describe such stem cell distribution in tissues. The interaction potential between a pair of stem cells decays exponentially with a characteristic length that spans several cell sizes, corresponding to the volume of cells generated per stem cell division. Our findings may help understanding the dynamics of normal and cancerous epithelial tissues.