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Elife. 2019 Jun 26;8. pii: e46735. doi: 10.7554/eLife.46735.

Metabolic constraints drive self-organization of specialized cell groups.

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InStem - Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India.
Simons Centre for the Study of Living Machines, National Centre for Biological Sciences-Tata Institute of Fundamental Research, Bangalore, India.
Manipal Academy of Higher Education, Manipal, India.


How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains unresolved. We find that within a mature, 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 self-assembly. Beginning in a uniformly gluconeogenic state, cells exhibiting a contrary, high pentose phosphate pathway activity state, spontaneously appear and proliferate, in a spatially constrained manner. Gluconeogenic cells in the colony produce and provide a resource, which we identify as trehalose. Above threshold concentrations of external trehalose, cells switch to the new metabolic state 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.


S. cerevisiae; cell biology; cell states; gluconeogenesis; pentose phosphate pathway; physics of living systems; self-organization; trehalose; yeast

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