Biology subjects

Nagasaki, M.

Publications and source records attributed to Nagasaki, M..

6 recordsLinked to original sources

bioRxiv2026

Inhibition of the gut ceramidase Asah2 decelerates the vertebrate ageing rate

The pace of ageing varies markedly among vertebrate species and individuals. However, the mechanisms underlying these differences in ageing rates remain unclear. Here, we show that the activity of the gut ceramidase Asah2 determines species- and strain-specific rates of vertebrate ageing. Comparative genomic analyses of vertebrate species and strains with different ageing rates reveal an association between low Asah2 activity and increased lifespan. Using the ultra-short-lived killifish Nothobranchius furzeri as a model, we demonstrate that knockout of Asah2 (asah2 KO) extends lifespan and attenuates systemic ageing phenotypes, including declines in locomotor activity, abnormal protein accumulation in the brain, and accumulation of senescent cells in the liver. asah2 KO elevates levels of ceramide species with long-chain fatty acids in the intestine, and supplementation with these ceramide species suppresses ageing phenotypes and extends lifespan in wild-type fish. asah2 KO and ceramide supplementation alter gut microbiota composition, and asah2 KO-derived microbiota transplantation attenuates ageing phenotypes, suggesting that reduced Asah2 activity prevents ageing through intestinal ceramide-mediated modulation of the microbiota. Given the evolutionary conservation of the Asah2 gene and its age-dependent upregulation in fish and humans, Asah2 and ceramides may act as ageing accelerators and decelerators, respectively, across animal species.

developmental biology↗

bioRxiv2024

Phased genome assemblies and pangenome graphs of human populations of Japan and Saudi Arabia

The selection of a reference sequence in genome analysis is critical, as it serves as the foundation for all downstream analyses. Recently, the pangenome graph has been proposed as a data model that incorporates haplotypes from multiple individuals. Here we present JaSaPaGe, a pangenome graph reference for Saudi Arabian and Japanese populations, both of which have been significantly underrepresented in previous genomic studies. We constructed JaSaPaGe from high-quality phased diploid assemblies which were made utilizing PacBio high-fidelity long reads, Nanopore long reads, and Hi-C short reads of 9 Saudi and 10 Japanese individuals. Quality evaluation of the pangenome graph by variant calling showed that our pangenome outperformed earlier linear reference genomes (GRCh38 and T2T-CHM13) and showed comparable performance to the pangenome graph provided by the Human Pangenome Reference Consortium (HPRC), with more variants found in Japanese and Saudi samples using their population-specific pangenomes. This pangenome reference will serve as a valuable resource for both the research and clinical communities in Japan and Saudi Arabia.

genomics↗

bioRxiv2024

MEGA-FISH: Multi-omics Extensible GPU-Accelerated FISH Processing Framework for Huge-Scale Spatial Omics

Spatial omics enables comprehensive mapping of cell types and states in their spatial context, providing profound insights into cellular communication and tissue organization. However, analyzing large tissue sections, especially crucial for clinical applications, remains a significant challenge due to the computational demands of current image processing methods. To overcome these limitations, we developed MEGA-FISH, a flexible, GPU-accelerated Python framework optimized for large-scale spatial omics image analysis. Benchmarking on simulated and tissue images demonstrated that MEGA-FISH achieved high accuracy in spot detection while significantly reducing processing times compared with established tools. The frameworks adaptable computational capabilities optimize resource allocation (e.g., GPU or multi-core CPU) for diverse tasks, and its scalable architecture enables integration with advanced imaging and segmentation techniques. By bridging cutting-edge imaging methods and single-cell analysis, MEGA-FISH provides an efficient platform for multi-modal analysis and advances research and clinical applications of spatial omics at organ and organism scales.

bioinformatics↗

bioRxiv2023

Precise immunofluorescence canceling for highly multiplexed imaging capturing specific cell state

Cell states are regulated by the response of signaling pathways to receptor ligand-binding and inter-cellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals. Here, we developed Precise Emission Canceling Antibodies (PECAbs) that have cleavable fluorescent labeling. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for reconstruction of the spatiotemporal dynamics of signaling pathways. Additionally, combining this approach with seq-smFISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system can serve as a comprehensive platform for analyzing complex cell processes.

cell biology↗

bioRxiv2020

A high fat containing chicken egg-only diet suppresses fatty liver induced by a lipid-rich methionine and choline deficient diet.

Nonalcoholic fatty liver disease (NAFLD) is a simple hepatic steatosis, which may proceed to nonalcoholic steatohepatitis (NASH) in the presence of steatosis and inflammation with hepatocyte injury. Obesity induced by a high-fat diet or high monosaccharide diet is considered a risk factor for NAFLD. A popular mouse model of NAFLD is a high-fat diet consisting of 60% energy from fat. A modified methionine and choline deficient (MCD) diet containing 60% energy from fat (CDAHFD) is a quick induction model for NAFLD. Chicken eggs also contain 60% energy from fat with very low carbohydrate. Here we compared liver pathologies in mice fed either a CDAHFD or egg-only diet. We found that a CDAHFD induced NAFLD within only two weeks.Ballooning of hepatocytes with an of immune cell appearance in the liver and high serum ALT and AST indicated that the mice fed CDAHFD developed NAFLD, which could proceed to NASH. However, mice fed an egg-only diet did not develop NAFLD even after 7 weeks. These mice showed normal liver histology with normal ALT and AST. The mice fed an egg-only diet showed high blood ketone bodies and normal blood glucose. Furthermore we found that the mice fed a combination CDAHFD /egg diet or mice fed an egg-only diet after two weeks of CDAHFD diet showed almost normal ALT and AST with reduced levels of fat bodies in the liver. These results indicate that an egg-only diet strongly inhibits high fat and carbohydrates induced NAFLD.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2019

3.5KJPNv2, An allele frequency panel of 3,552 Japanese Individuals

The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels and to provide them through easy-to-use interfaces. In the Tohoku Medical Megabank Project, we have sequenced nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first largescale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.

genomics↗