Biomedical subjects

Chikara Furusawa

Publications and source records attributed to Chikara Furusawa.

10 recordsLinked to original sources

PubMed2006

Evolutionary origin of power-laws in a biochemical reaction network: embedding the distribution of abundance into topology.

The evolutionary origin of general statistics in a biochemical reaction network is studied here to explain the power-law distribution of reaction links and the power-law distribution of chemical abundance. Using cell models with catalytic reaction networks, we have confirmed that the power-law distribution for the abundance of chemicals emerges by the selection of cells with higher growth rates, as suggested in our previous study [Phys. Rev. Lett. 90, 088102 (2003)]. Through further evolution, this inhomogeneity in chemical abundance is shown to be embedded in the distribution of links, leading to the power-law distribution. We analyze the mechanism of this embedding and discuss the generality of the results.

Journal Article↗

PubMed2006

Precise metabolic flux analysis of coryneform bacteria by gas chromatography-mass spectrometry and verification by nuclear magnetic resonance.

Precise metabolic flux analysis (MFA) by gas chromatography-mass spectrometry (GC-MS) and computer calculation was performed, and the consistency of the estimated results was verified by independently performed nuclear magnetic resonance (NMR) analysis. The precise estimation of flux by the integration method of the mass isotopomer signal, defined as the coefficient of variance (CV) of multiple determination, was investigated, and the results estimated using different data sets with the same magnitude of error were confirmed. The CV of multiple determinations was sufficiently small to discuss and compare the fluxes of a metabolic pathway. The estimated fluxes using the GC-MS data were cross-validated with the NMR data that were independently measured and not used for MFA. The developed method was successfully applied to the MFA of the growth phase of two different glutamate-producing coryneform bacteria, Corynebacterium glutamicum and C. efficiens. The difference in the growth rate between these two bacterial species was discussed while considering the results of MFA, including forward and backward (exchange) fluxes.

Actinomycetales↗

PubMed2006

Morphogenesis, plasticity and irreversibility.

The dynamical systems theory of morphogenesis is surveyed, in which positional information is generated through intracellular reaction dynamics and cell-cell interaction. Cells differentiate because of these dynamics. In addition, these differentiated cells form an ordered spatial pattern, which further stabilizes the cellular states, leading to robust morphogenesis and irreversibility in the differentiation. Induction, community effect, gastrulation and activin-controlled artificial tissue-genesis are discussed from the perspective of this theory and the relevance of dynamics of cellular plasticity is stressed.

Animals↗

PubMed2005

An evolutionary relationship between genetic variation and phenotypic fluctuation.

The relevance of phenotype fluctuations among clones (i.e., organisms with identical genes) to evolution has recently been recognized both theoretically and experimentally. By considering the stability of the distributions of genetic variations and phenotype fluctuations, we derive a general inequality between the phenotype variance due to genetic differences and the intrinsic phenotype variance of clones. For a given mutation rate, an approximately linear relationship between the two is obtained which elucidates the consistency between the fundamental theorem of natural selection by Fisher and the evolutionary fluctuation-response relationship (fluctuation dissipation theorem) proposed recently. A general condition for the error catastrophe is also derived as the violation of the inequality, which sets up the limit to the speed of stable evolution. All of these theoretical results are confirmed by a numerical evolution experiment of a cell that consists of a catalytic reaction network. Based on the relationships proposed here, relevance of the phenotypic plasticity to evolution as well as the genetic assimilation is discussed.

Animals↗

PubMed2005

Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture.

Bipotent mesendoderm that can give rise to both endoderm and mesoderm is an established entity from C. elegans to zebrafish. Although previous studies in mouse embryo indicated the presence of bi-potent mesendoderm cells in the organizer region, characterization of mesendoderm and its differentiation processes are still unclear. As bi-potent mesendoderm is implicated as the major precursor of definitive endoderm, its identification is also essential for exploring the differentiation of definitive endoderm. In this study, we have established embryonic stem (ES) cell lines that carry GFP gene in the goosecoid (Gsc) gene locus and have investigated the differentiation course of mesendodermal cells using Gsc expression as a marker. Our results show that mesendoderm is represented as a Gsc-GFP+ E-cadherin(ECD)+ PDGFRalpha(alphaR)+ population and is selectively induced from ES cells under defined conditions containing either activin or nodal. Subsequently, it diverges to Gsc+ ECD+ alphaR- and Gsc+ ECD- alphaR+ intermediates that eventually differentiate into definitive endoderm and mesodermal lineages, respectively. The presence of mesendodermal cells in nascent Gsc+ ECD+ alphaR+ population was also confirmed by single cell analysis. Finally, we show that the defined culture condition and surface markers developed in this study are applicable for obtaining pure mesendodermal cells and their immediate progenies from genetically unmanipulated ES cells.

Activins↗

PubMed2004

Selection of initial conditions for recursive production of multicellular organisms.

The development of a multicellular organism is a dynamic process. Starting from one or a few cells, the organism becomes a set of cells with different types that form well-determined patterns. It is rather surprising that differentiation in cell types and formation of controlled patterns are compatible, because the former gives morphogenetic diversification whereas the latter implies recursive production of a cell ensemble, reducing individual differences. We studied this problem by taking a simple cell model with intracellular reaction dynamics of chemical concentrations, cell-cell interactions, and increase in cell numbers. We observed successive differentiation from a cell type with diverse chemicals and chaotic concentration dynamics to cell types with oscillatory or fixed-point dynamics, leading to morphogenetic diversity in a spatial pattern. We further show that, by starting from an initial object consisting of both the former cell type with diverse chemicals and the latter differentiated cell type, the recursive production of a multicellular organism with morphogenetic diversity is possible. By relating the former type to a cell in the vegetal pole and the latter to one in the animal pole, classic experimental results with separation of blastomeres in sea urchin eggs are coherently explained, while some predictions are made for in vitro morphogenesis from embryonic stem cells.

Animals↗

PubMed2004

Global change in Escherichia coli gene expression in initial stage of symbiosis with Dictyostelium cells.

Genome-wide gene expression profiling was performed to investigate the early formation of symbiosis using an artificial symbiosis of Escherichia coli and Dictyostelium discoideum. We have previously reported that when these two species were allowed to grow on minimal agar plates, they achieved a stable state of coexistence, in which the emerging E. coli colonies housing Dictyostelium cells were of a mucoidal nature that was not observed originally. We used this microbiological system as a model to study the initial stages of the development of the symbiotic relationship. The E. coli gene expression profiles of symbiotic cells and non-symbiotic cells captured using GeneChip technology were compared. It was clearly shown that the gene expression profile was substantially altered in E. coli cells undergoing symbiotic transition. The genes responsible for central energy metabolism as well as those responsible for translation apparatus were down-regulated in symbiotic E. coli. The transcriptional patterns of genes coding for the E. coli cell surface structure were drastically altered, and this alteration may determine the mucoidal nature and unique structure of coexisting colonies. General stress inducible genes were expressed at low levels in symbiotic E. coli. These observed changes in the transcription profile indicate that the central metabolism of symbiotic E. coli is attenuated as a whole, and the cells are probably under less stress because of the benefits brought by coexistence with the symbiotic counterpart Dictyostelium.

Animals↗

PubMed2003

Robust development as a consequence of generated positional information.

The origin and robustness of morphogenesis are studied by dynamical system modeling of a cell society, in which cells possessing internal chemical reaction dynamics interact with each other through their mutual interaction with diffusive chemicals in a two-dimensional medium. It is found that stem-type cells differentiate into various cell types (where a cell 'type' is defined by a type of intra-cellular dynamics) due to a dynamic instability caused by cell-cell interactions in a manner described by the isologous diversification theory. The differentiations are spatially regulated by the concentration of chemicals in the medium, while the chemical concentrations are locally influenced by the intra-cell dynamics. Through this reciprocal relationship, chemical concentrations come to exhibit spatial variation as differentiated cell types begin to emerge, and as a result the regulation exercised by the chemical concentrations become spatially inhomogeneous. This reinforces the process of differentiation, through which spatial patterns of differentiated cells appear. Within this reciprocal relationship, the concentration gradients are read and interpreted by the cell as positional information. A spatial order of cells realized in this process represents a stable state of the system governed by this reciprocal relationship, and that the developmental process through which this state is realized is robust with respect to perturbations. The dependence of the morphogenesis on history and the community effect in cell differentiation are also discussed.

Animals↗

PubMed2003

Zipf's law in gene expression.

Using data from gene expression databases on various organisms and tissues, including yeast, nematodes, human normal and cancer tissues, and embryonic stem cells, we found that the abundances of expressed genes exhibit a power-law distribution with an exponent close to -1; i.e., they obey Zipf's law. Furthermore, by simulations of a simple model with an intracellular reaction network, we found that Zipf's law of chemical abundance is a universal feature of cells where such a network optimizes the efficiency and faithfulness of self-reproduction. These findings provide novel insights into the nature of the organization of reaction dynamics in living cells.

Animals↗

PubMed2002

Origin of multicellular organisms as an inevitable consequence of dynamical systems.

The origin of multicellular organisms is studied by considering a cell system that satisfies minimal conditions, that is, a system of interacting cells with intracellular biochemical dynamics, and potentiality in reproduction. Three basic features in multicellular organisms-cellular diversification, robust developmental process, and emergence of germ-line cells-are found to be general properties of such a system. Irrespective of the details of the model, such features appear when there are complex oscillatory dynamics of intracellular chemical concentrations. Cells differentiate from totipotent stem cells into other cell types due to instability in the intracellular dynamics with cell-cell interactions, as explained by our isologous diversification theory (Furusawa and Kaneko, 1998a; Kaneko and Yomo, 1997). This developmental process is shown to be stable with respect to perturbations, such as molecular fluctuations and removal of some cells. By further imposing an adequate cell-type-dependent adhesion force, some cells are released, from which the next generation cell colony is formed, and a multicellular organism life-cycle emerges without any finely tuned mechanisms. This recursive production of multicellular units is stabilized if released cells are few in number, implying the separation of germ cell lines. Furthermore, such an organism with a variety of cellular states and robust development is found to maintain a larger growth speed as an ensemble by achieving a cooperative use of resources, compared to simple cells without differentiation. Our results suggest that the emergence of multicellular organisms is not a "difficult problem" in evolution, but rather is a natural consequence of a cell colony that can grow continuously.

Algorithms↗