The embryo game uncovers hidden cell behaviours.

Abstract

While cells are driven to preserve their own survival, they must cooperate to ensure embryo viability. To explore how cellular behaviours shape human development, we intersect evolutionary game theory and in vitro embryo modelling. We focus on cell competition, a conserved cell-cell killing thought to enable embryonic error correction, though few studies directly link it to embryo success. Our collective risk game shows that killing is costly for a cell, but beneficial when the embryo exceeds its target size and the probability of survival is low. Analogously, successful heX-embryoids form within the target size range of the native human embryonic disc and inhibiting cell death produces larger, defective embryoids. Killing and proliferating are responsive cellular behaviours that maintain optimal embryoid size, consistent with their emergence as conditional strategies in our game. Further, conditional killing is a "threat" to restrain over-proliferating cells. Counter-intuitively, cell competition may underpin cooperation in the embryo.