Large-Scale Survey of Cell-Differentiation Programs in a Generative Model Reveals Regeneration as an Epiphenomenon of Development

Development combines three basic processes asymmetric --- cell division, signaling and gene regulation --- in a multitude of ways to create an overwhelming diversity of multicellular life-forms. Here, we attempt to chart this diversity using a generative model. We sample millions of biologically feasible developmental schemes, allowing us to comment on the statistical properties of cell-differentiation trajectories they produce. Our results indicate that, in contrast to common views, cell-type lineage graphs are unlikely to be tree-like. Instead, they are more likely to be directed acyclic graphs, with multiple lineages converging on the same terminal cell-type. Additionally, in line with the hypothesis that whole body regeneration is an epiphenomenon of development, a majority of the `organism' generated by our model can regenerate using pluripotent cells. The generative framework is modular and flexible, and can be adapted to test additional hypotheses about general features of development.

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