Life in the trenches: spatial confinement induces evolutionary pattern formation*

As cells divide in somatic tissues, multiple clonal groups with distinct mutations may arise in parallel. The physical properties of somatic tissues that influence the evolutionary dynamics of these clones remain largely unexplored. Here, we study the effect of tissue dimensions and geometry. Using stochastic simulations, we show that spatial confinement aligns boundaries between stem cell clones to the confined dimension with clones regularly spaced along the longer axis, forming patterns reminiscent of phase separation. The patterns emerge only as the confinement shrinks below a critical length, which is on the order of a few hundred cell sizes, a scale relevant to many physiological processes. We observed that under spatial confinement, clones spread more slowly and coexist as competing lineages. To determine if our observations can apply to more complex tissues, we extend this model to explicitly incorporate cell differentiation. With differentiated cells acting as buffers between stem cells, the clonal patterns are preserved but their intrinsic length scale increases. Altogether, we predict that the spatial arrangement of cells significantly alters their evolutionary dynamics in tissues.