RT Journal Article
SR Electronic
T1 Large-Scale Survey of Cell-Differentiation Programs in a Generative Model Reveals Regeneration as an Epiphenomenon of Development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 843888
DO 10.1101/843888
A1 Somya Mani
A1 Tsvi Tlusty
YR 2019
UL http://biorxiv.org/content/early/2019/12/29/843888.abstract
AB 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 ‘organisms’ 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.