Biology subjects

Tsuchiya, M.

Publications and source records attributed to Tsuchiya, M..

26 records · Page 2Linked to original sources

bioRxiv2020

Massive occurrence of benthic plastic debris at the abyssal seafloor beneath the Kuroshio Extension, the North West Pacific

The deep-sea is considered to be an ultimate sink for marine plastic debris. The abyssal (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. We undertook a quantitative assessment of debris presents on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific, which is one of the major transit points for massive amounts of debris sourced from Asia that are entering the North Pacific Ocean. The dominant type of debris was single-use plastics-mainly bags and food packaging. The density of plastic debris (average 4561 items km-2) in the abyssal zone was the highest recorded for an abyssal plain, suggesting that the deep-sea basin of the Northwest Pacific is a significant reservoir of plastic debris.

ecology↗

bioRxiv2020

Translational control of methionine and serine metabolic pathways underpin the paralog-specific phenotypes of Rpl22 ribosomal protein mutants in cell division and replicative longevity

A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Some may reflect general effects due to lower growth rate and ribosome levels, but a number of diverse phenotypes cannot be explained through this mechanism. Yeast and other organisms live longer when they lack specific ribosomal proteins, especially of the large 60S subunit of the ribosome. However, longevity is neither associated with the generation time of RP deletion mutants nor with bulk inhibition of protein synthesis. Here, we comprehensively queried actively dividing RP paralog mutants through the cell cycle. Our data link transcriptional, translational, and metabolic changes to phenotypes associated with the loss of paralogous RPs. We uncovered specific translational control of transcripts encoding enzymes of methionine and serine metabolism, which are part of one-carbon (1C) pathways. Cells lacking Rpl22Ap, which are long-lived, have lower levels of metabolites associated with 1C metabolism. Loss of 1C enzymes, such as the serine hydroxymethyltransferase Shm2p increased the longevity of wild type cells. These results provide a molecular basis for paralog-specific phenotypes in ribosomal mutants and underscore the significance of 1C metabolic pathways in mechanisms of cell division and cellular aging. 1C pathways exist in all organisms, including humans, and targeting the relevant enzymes could represent longevity interventions.

molecular biology↗

bioRxiv2019

Self-Organization of Whole Gene Expression through Coordinated Chromatin Structural Transition: Validation of Self-Organized Critical Control of Genome Expression

Through our studies on whole genome regulation, we have demonstrated the existence of self-organized critical control (SOC) of whole gene expression - genomic self-organization mechanism through the emergence of a critical point (CP) at both the cell population and single cell level. In this paper, based on HRG and EGF-stimulated MCF-7 breast-cancer cell line, we shed light on the origin of critical transitions stemming from coordinated chromatin remodeling. In so doing, we validated the core of the SOC control mechanism through the application of a non-linear signal analysis technique (Recurrence Quantification Analysis: RQA), and of Principal Component Analysis (PCA). The main findings were: O_LITranscriptional co-regulation follows a strong and invariant exponential decay as between gene spacing along the chromosome is increased. This shows that the co-regulation occurs on a mainly positional basis reflecting local chromatin organization. C_LIO_LIThere are two main fluctuation modes on the top of the cell-kind specific gene expression values spanning the entire genome expression. These modes establish an autonomous genomic critical control system (genome-engine) through the activation of the CP for cell-fate guiding critical transitions revealed by SOC analysis. C_LI The elucidation of the link between spatial position on chromosome and co-regulation together with the identification of specific locations on the genome devoted to the generalization of perturbation stimuli, give a molecular basis to the self-organization dynamics of genome expression and cell-fate decision.

genomics↗

bioRxiv2019

Phenotypic and genotypic consequences of CRISPR/Cas9 editing of the replication origins in the rDNA of Saccharomyces cerevisiae

The complex structure and repetitive nature of eukaryotic ribosomal DNA (rDNA) is a challenge for genome assembly, and thus, the consequences of sequence variation in rDNA remain unexplored. However, renewed interest in the role that rDNA variation may play in diverse cellular functions, aside from ribosome production, highlights the need for a method that would permit genetic manipulation of the rDNA. Here, we describe a CRISPR/Cas9 based strategy to edit the rDNA locus in the budding yeast Saccharomyces cerevisiae. Using this approach, we modified the endogenous rDNA origin of replication in each repeat by deleting or replacing its consensus sequence. We characterized the transformants that have successfully modified their rDNA locus and propose a mechanism for how CRISPR/Cas9 mediated editing of the rDNA occurs. In addition, we carried out extended growth and life span experiments to investigate the long-term consequences that altering the rDNA origin of replication has on cellular health. We find that long-term growth of the edited clones results in faster growing suppressors that have acquired segmental aneusomy of the rDNA containing region of chr XII or aneuploidy of chromosomes XII, II, or IV. Furthermore, we find that all edited isolates suffer a reduced life span, irrespective of their levels of extrachromosomal rDNA circles. Our work demonstrates that it is possible to quickly, efficiently and homogeneously edit the rDNA locus via CRISPR/Cas9. It serves as a model for modifying other parts of the rDNA and, more generally, for editing other tandemly repeated sequences in higher eukaryotes.

genetics↗

bioRxiv2019

Underlying Genomic Mechanism for Cell-Fate Change from Embryo to Cancer Development

The elucidation of the how and when of a cell-fate change asks for a physically reasonable mechanism allowing to achieve a coordinated switching of thousands of genes within a small and highly packed cell nucleus. We previously demonstrated that whole genome expression is dynamically self-organized through the emergence of a critical point. Furthermore, it has been confirmed that this happens at both the cell-population and single-cell level through the physical principle of self-organized criticality. In this paper, we further examine the genomic mechanism which determines cell-fate changes from embryo to cancer development. The state of the critical point, acting as the organizing center of cell-fate, determines whether the genome resides in a super- or sub-critical state. In the super-critical state, a specific stochastic perturbation can spread over the entire system through the genome engine - an autonomous critical-control genomic system, whereas in the sub-critical state, the perturbation remains at a local level. We provide a consistent framework to develop a biological regulation transition theory demonstrating the cell-fate change.

cell biology↗

bioRxiv2018

Self-Organized Critical Control of Genome Expression: Novel Scenario on Cell-Fate Decision

In our current studies on whole genome expression in several biological processes, we have demonstrated the actual existence of self-organized critical control (SOC) of gene expression at both population and single cell level. SOC allows for cell-fate change by critical transition encompassing the entire genome expression that, in turn, is partitioned into distinct response domains (critical states).\n\nIn this paper, we go more in depth into the elucidation of SOC control of genome expression focusing on the determination of critical point (CP) and associated distinct critical states in single-cell genome expression. This leads us to the proposal of a potential universal model with genome-engine mechanism for cell-fate change. Our findings suggest that the CP is fixed point in terms of temporal expression variance, where the CP (set of critical genes) becomes active (ON) for cell-fate change ( super-critical in genome-state) or else inactive (OFF) state ( sub-critical in genome-state); this may lead to a novel scenario of the cell-fate control through activating or inactivating CP.

genomics↗

bioRxiv2017

Single-Cell Reprogramming Of Mouse Embryo Development Through A Critical Transition State

Our work dealing with the temporal development of the genome-expression profile in single-cell mouse early embryo indicated that reprogramming occurs via a critical transition state, where the critical-regulation pattern of the zygote state disappears. In this report, we unveil the detailed mechanism of how the dynamic interaction of thermodynamic states (critical states) enables the genome system to pass through the critical transition state to achieve genome reprogramming.\n\nSelf-organized criticality (SOC) control of overall expression provides a snapshot of self-organization and explains the coexistence of critical states at a certain experimental time point. The time-development of self-organization is dynamically modulated by exchanges in expression flux between critical states through the cell nucleus milieu, where sequential global perturbations involving activation-inhibition of multiple critical states occur from the early state to the late 2-cell state. Two cyclic fluxes act as feedback flow and generate critical-state coherent oscillatory dynamics. Dynamic perturbation of these cyclic flows due to vivid activation of the ensemble of low-variance expression (sub-critical state) genes allows the genome system to overcome a transition state during reprogramming.\n\nOur findings imply that a universal mechanism of long-term global RNA oscillation underlies autonomous SOC control, and the critical gene ensemble at a critical point (CP) drives genome reprogramming. Unveiling the corresponding molecular players will be essential to understand single-cell reprogramming.

developmental biology↗

bioRxiv2017

Single-Cell Statistical Thermodynamics In Early Embryo Development

A statistical thermodynamics approach to the temporal development of biological regulation provides a phenomenological description of the dynamical behavior of genome expression in terms of autonomous self-organization with a critical transition (Self-Organized Criticality: SOC). In early mouse embryo development, the dynamical change in the self-organization of overall expression determines how and when reprogramming of the genome-expression state occurs. Reprogramming occurs via a transition state (climbing over an epigenetic landscape), where the critical-regulation pattern of the zygote state disappears. A critical transition is well captured in terms of the bimodality of expression ensembles, which reflects distinct thermodynamic states (critical states). These critical states exhibit a genome avalanche pattern: competition between order (scaling) and disorder (divergence) around a critical point. The genome avalanche in mouse embryo development, which is committed to erase a previous ordered state, reveals that the direction of early embryo single-cell development traverses the same steps as in differentiation, but in the opposite order of self-organization.

genomics↗