RT Journal Article SR Electronic T1 Metabolic constraints drive self-organization of specialized cell groups JF bioRxiv FD Cold Spring Harbor Laboratory SP 573626 DO 10.1101/573626 A1 Sriram Varahan A1 Adhish Walvekar A1 Vaibhhav Sinha A1 Sandeep Krishna A1 Sunil Laxman YR 2019 UL http://biorxiv.org/content/early/2019/03/11/573626.abstract AB How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains an unresolved question. We find that within a clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such assembly. Beginning in a gluconeogenic state, cells in a contrary state, exhibiting high pentose phosphate pathway activity, spontaneously appear and proliferate, in a spatially constrained manner. The gluconeogenic cells in the developing colony produce a resource, which we identify as trehalose. At threshold concentrations of trehalose, cells in the new metabolic state emerge and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states.