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Commun Integr Biol. 2012 Jul 1;5(4):393-4. doi: 10.4161/cib.20310.

Tunability of the ratio of cell states after the synthetic diversification by the diversity generator.

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Department of Computational Intelligence and Systems Science; Tokyo Institute of Technology; Kanagawa, Japan.


The autonomous generation of phenotypic diversity in embryonic cell populations can be explained by Waddington's landscape. The landscape proposes that intra- and inter-cellular interactions mediate the generation of cellular diversity. Recently, we implemented, in a population of Escherichia coli, a synthetic diversification, which is governed by inter-cellular signaling mediated by acyl-homoserine lactone (AHL). The cells with the diversity generator diversified into two distinct cell states, "high" and "low," if all of the cells started from the low state. The ratio of the states after the diversification was affected by the velocity of autonomous signal accumulation, which depends on the cell density and the AHL production rate of individual cells. The dependency of the ratio on the initial cell density is reminiscent of the community effect, which is observed in animal development and is important for ES-cell differentiation. Therefore, it is worthwhile reviewing the roles of natural animal gene networks with similar topologies to the diversity generator design. The diversity generator design will also be the basis for a tool to direct cell fates on the population level in tissue engineering. Here, we discuss the tunability of the ratio of cell states by our synthetic circuit design.


Waddington epigenetic landscape; bifurcation; bioengineering; community effect; inter-cellular signaling; phenotypic diversification; synthetic biology; tissue engineering

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