Metabolic constraints drive self-organization of specialized cell groups

  1. Sriram Varahan
  2. Adhish Walvekar
  3. Vaibhhav Sinha
  4. Sandeep Krishna
  5. Sunil Laxman  Is a corresponding author
  1. InStem - Institute for Stem Cell Science and Regenerative Medicine, India
  2. National Centre for Biological Sciences­‐Tata Institute of Fundamental Research, India

Abstract

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.

Data availability

All data in this study are generated by computational simulations. All model parameters and equations are included in the manuscript and source code is included with this submission.

Article and author information

Author details

  1. Sriram Varahan

    InStem - Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Adhish Walvekar

    InStem - Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7344-7653
  3. Vaibhhav Sinha

    Simons Centre for the Study of Living Machines, National Centre for Biological Sciences­‐Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5169-5485
  4. Sandeep Krishna

    Simons Centre for the Study of Living Machines, National Centre for Biological Sciences­‐Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Sunil Laxman

    InStem - Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
    For correspondence
    sunil.laxman@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0861-5080

Funding

Wellcome Trust - DBT India Alliance (IA/I/14/2/501523)

  • Sunil Laxman

Simons Foundation

  • Vaibhhav Sinha
  • Sandeep Krishna

Wellcome Trust - DBT India Alliance (IA/E/16/1/502996)

  • Sriram Varahan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Varahan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sriram Varahan
  2. Adhish Walvekar
  3. Vaibhhav Sinha
  4. Sandeep Krishna
  5. Sunil Laxman
(2019)
Metabolic constraints drive self-organization of specialized cell groups
eLife 8:e46735.
https://doi.org/10.7554/eLife.46735

Share this article

https://doi.org/10.7554/eLife.46735

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