Title: Dearth of tree-type lineage maps and emergence of pluripotency in a minimal generative model of biological development

Abstract: To transform a single-celled zygote into an adult multicellular organism, development employs three basic processes — asymmetric cell division, signalling and gene regulation. The huge variety of multicellular life-forms emphasizes the overwhelming diversity that combinations of these three processes can create. Here, we attempt to chart this diversity using a generative, rule-based model that uses these basic developmental processes as its minimal ingredients. We sample millions of developmental schemes and survey the variety of cell-type lineage graphs they produce. Our collection of lineage graphs allows us to comment on the statistical properties of cell-differentiation trajectories expected in real biological organisms. 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 cell 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 ‘organisms’ generated by our model can regenerate using pluripotent cells.