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

Abstract

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.

Keywords: :

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

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Acknowledgments

This work was supported by the Precursory Research for Embryonic Science and Technology program of Japan Science and Technology to D.K. and the Grant-in-Aid for Scientific Research (KAKENHI) programs from Ministry of Education, Culture, Sports, Science, and Technology (#14085101 to M.H.; #14085203 to M.Y. and D.K.; #23119005 to D.K.; and #23119008 to M.Y.) and Japan Society for the Promotion of Science (#21650018 to M.H. and D.K.; and #23680031 to D.K.). We thank Masahiro Takinoue and other members of the group for helpful discussions.