|DATE||November 09 (Mon), 2020|
|TITLE||[GS_C_BSM] A generative model of biological development reveals remarkable pluripotency and diverse topologies of cell lineage graphs|
To transform a single-celled zygote into an adult multicellular organism, development employs three basic processes --- asymmetric cell division, signaling and gene regulation. The multitude of multicellular life-forms we see today 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 systematically survey the variety of cell-type lineage graphs they produce. Our extensive collection of lineage graphs allows us to comment on the statistical properties of cell-differentiation trajectories 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. The framework of our model is modular and flexible, and allows modifications to test additional hypotheses and illustrate universal features of development.