Temporal competition between differentiation programs determines cell fate choice

Anna Kuchina, Lorena Espinar, Tolga Çaǧatay, Alejandro O. Balbin, Fang Zhang, Alma Alvarado, Jordi Garcia-Ojalvo, Gürol M. Süel

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Abstract

Multipotent differentiation, where cells adopt one of several possible fates, occurs in diverse systems ranging from bacteria to mammals. This decision-making process is driven by multiple differentiation programs that operate simultaneously in the cell. How these programs interact to govern cell fate choice is poorly understood. To investigate this issue, we simultaneously measured activities of the competing sporulation and competence programs in single Bacillus subtilis cells. This approach revealed that these competing differentiation programs progress independently without cross-regulation before the decision point. Cells seem to arrive at a fate choice through differences in the relative timing between the two programs. To test this proposed dynamic mechanism, we altered the relative timing by engineering artificial cross-regulation between the sporulation and competence circuits. Results suggest a simple model that does not require a checkpoint or intricate cross-regulation before cellular decision-making. Rather, cell fate choice appears to be the outcome of a 'molecular raceg' between differentiation programs that compete in time, providing a simple dynamic mechanism for decision-making.

Original languageEnglish (US)
Article number557
JournalMolecular Systems Biology
Volume7
DOIs
StatePublished - Dec 19 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Kuchina, A., Espinar, L., Çaǧatay, T., Balbin, A. O., Zhang, F., Alvarado, A., Garcia-Ojalvo, J., & Süel, G. M. (2011). Temporal competition between differentiation programs determines cell fate choice. Molecular Systems Biology, 7, [557]. https://doi.org/10.1038/msb.2011.88