RIKEN Center for Biosystems Dynamics Research (BDR)

A dynamical system model of stem cell differentiation

One important issue in developmental biology is the understanding of those characteristics that distinguish multipotent stem cells from differentiated cell types; in other words, how do cells know when to proliferate and when to differentiate? We have performed computer simulations of the developmental process to screen for the gene regulatory networks that can generate cell-type diversity through stem cell differentiations. We found that those stem cells that both proliferate and differentiate always exhibit oscillatory expression dynamics, and that regulating the differentiation frequency of these stem cells causes a robust number distribution of cell types. These findings can explain the recently observed heterogeneity and dynamic equilibrium of the cellular states in stem cells (Furusawa and Kaneko, Science 2012; Suzuki, Furusawa and Kaneko, PLoS One 2011).

Analysis of phenotypic memory in bacterial experiental evolution

Technological advances have made it possible to reveal the phenotypic and genetic changes responsible for adaptive evolution. In this study, we performed parallel evolution experiments of Escherichia coli under ethanol stress for 1000 generations to obtain ethanol tolerant strains. Transcriptome and metabolite analyses revealed that the phenotypic changes were almost identical among all tolerant strains. We also found that the numbers of fixed mutations in these strains were less than 10 and there were few overlaps. These results suggest that the observed phenotypic changes were not caused by genomic mutations, but instead were the result of an epigenetic memory which has a much longer time-scale than their generation time and contributes to the phenotypic changes of ethanol tolerance.

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