PT  - JOURNAL ARTICLE
AU  - Sriram Varahan
AU  - Adhish Walvekar
AU  - Vaibhhav Sinha
AU  - Sandeep Krishna
AU  - Sunil Laxman
TI  - Metabolic constraints drive self-organization of specialized cell groups
AID  - 10.1101/573626
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 573626
4099  - http://biorxiv.org/content/early/2019/03/11/573626.short
4100  - http://biorxiv.org/content/early/2019/03/11/573626.full
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.