Emergent order in epithelial sheets by interplay of cell divisions and cell fate regulation

Abstract

The fate choices of stem cells between self-renewal and differentiation are often tightlyregulated by paracrine (cell-cell) signalling. Here, we assess how the interplay between division, differentiation, and short range paracrine signalling can affect the macroscopic ordering of cell types in self-renewing epithelial sheets, by studying a simple spatial cell fate model with cells being arranged on a 2D lattice. We show in this model that if cells commit to their fate directly upon cell division, macroscopic domains of cells of the same type emerge, if at least a small proportion of divisions are symmetric, except if signalling interactions are laterally inhibiting. In contrast, if cells are first 'licensed' to differentiate,
yet retaining the possibility to return to their naive state, macroscopic order only emerges if the signalling strength exceeds a critical threshold: if then the signalling interactions are laterally inducing, macroscopic domains emerge as well. Lateral inhibition, on the other hand, can in that case generate macroscopic patterns of alternating cell types (checkerboard pattern), yet only if the proportion of symmetric divisions is sufficiently low. These results can be understood theoretically by an analogy to phase transitions in spin systems known from statistical physics.

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ORCID for Philip Greulich: orcid.org/0000-0001-5247-6738

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