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Local mechanical gradients underlie coordinated cascades of epithelial cell-cycle advance

Shoham Wanszelbaum, Areej Saleem, Liav Daraf, Yael Lavi, Lior AtiaiD

Abstract

Cell division mechanically perturbs the local environment in epithelial tissues, yet whether and how these perturbations propagate to coordinate cell-cycle progression across neighboring cells remains unclear. Here, we combine live cell-cycle tracking with mechanical analysis to examine how division events organize in space and time. We find that coordinated changes and spatial gradients in forces, morphology, and dynamics precede synchronized G1[->]S transitions in nearby cells. These transitions emerge within localized high-tension zones and give rise to spatiotemporal clusters of cell divisions, indicating that division events are mechanically coupled and propagate across neighboring cells. Supporting this biophysical picture, similar mechanical patterns arising from cell extrusion are sufficient to induce cell-cycle re-entry in neighboring cells. Together, these findings suggest a mechanically mediated framework for coordinated proliferation, possibly driven by positive mechanical feedback.

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