A5021141087- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Renal Diseases and Glomerulopathies
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Cell Adhesion Molecules Research
- Pluripotent Stem Cells Research
- Hydraulic flow and structures
- Amino Acid Enzymes and Metabolism
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Gene Regulatory Network Analysis
- Glycosylation and Glycoproteins Research
- Endoplasmic Reticulum Stress and Disease
- Single-cell and spatial transcriptomics
- Diabetes Management and Research
- Extracellular vesicles in disease
- Fatty Acid Research and Health
- Microbial infections and disease research
- Proteoglycans and glycosaminoglycans research
- Cavitation Phenomena in Pumps
National Center for Global Health and Medicine
2016-2025
Center for Global Health
2021-2024
University of Tsukuba
2021-2024
Kyoto Prefectural University of Medicine
2021
Juntendo University
2021
Shinshu University
2021
Eisai (Japan)
2021
RIKEN BioResource Research Center
2021
Kitasato University
1995-2020
Institute of Laboratory Animal Science
2013-2017
Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, mechanism underlying regulation transcriptional kinetics (burst size frequency) mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing analyze intrinsic noise mRNA levels for elucidating mouse embryonic stem cells. Informatics analyses functional assays revealed that was regulated by a combination...
Osteoprotegerin (OPG) is a circulating decoy receptor for RANKL, multifunctional cytokine essential the differentiation of tissue-specific cells in bone and immune systems such as osteoclasts, medullary thymic epithelial (mTECs), intestinal microfold (M cells). However, it unknown whether OPG functions only at production site or circulates to other tissues acting an endocrine fashion. Here we explore cellular source by generating OPG-floxed mice show that locally produced OPG, rather than...
Abstract COVID-19 caused by SARS-CoV-2 has continually been serious threat to public health worldwide. While a few anti-SARS-CoV-2 therapeutics are currently available, their antiviral potency is not sufficient. Here, we identify two orally available 4-fluoro-benzothiazole-containing small molecules, TKB245 and TKB248, which specifically inhibit the enzymatic activity of main protease (M pro ) significantly more potently block infectivity replication various strains than nirmatrelvir,...
Abstract The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease humans, immune cells accumulate oral mucosa promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression osteogenic such as osteoblasts periodontal ligament cells. However, detailed mechanism underlying immune–bone periodontitis is not fully understood. Here, we performed single-cell RNA-sequencing analysis on...
Type 2 diabetes is a multifactorial disease caused by insulin resistance and impaired secretion from pancreatic β-cells, but the precise mechanisms remain to be elucidated. To identify primary genetic factors of type in rat model, we performed comparative transcriptome mutation analyses islets between obese Zucker fatty rat-derived model ZFDM rat. Among differentially expressed genes irrespective obesity glucose intolerance states, identified nonsense mutation, c.409C>T (p.Gln137X),...
Tendons are connective tissues that join muscles and bones rich in glycosaminoglycans (GAGs). Decorin is a proteoglycan with one dermatan sulfate (DS) or chondroitin (CS) chain (a type of GAG) attached to its core protein involved regulating the assembly collagen fibrils tendon extracellular matrix (ECM). Calcium-activated nucleotidase 1 (CANT1), hydrolyzes uridine diphosphate into monophosphate phosphate, plays an important role GAG synthesis cartilage. In present study, we performed...
γδT cells produce inflammatory cytokines and have been implicated in the pathogenesis of cancer, infectious diseases, autoimmunity. The T cell receptor (TCR) signal transduction that specifically regulates development IL-17–producing (γδT17) largely remains unclear. Here, we showed proximal tyrosine kinase Syk is essential for γδTCR γδT17 mouse thymus. Zap70, another αβT cells, failed to functionally substitute γδT17. induced activation PI3K/Akt pathway upon stimulation. Mice deficient PI3K...
Potent and biostable inhibitors of the main protease (Mpro) SARS-CoV-2 were designed synthesized based on an active hit compound 5h (2). Our strategy was not only introduction fluorine atoms into inhibitor molecule for increase binding affinity pocket Mpro cell membrane permeability but also replacement digestible amide bond by a surrogate structure to biostability compounds. Compound 3 is highly potent blocks infection in vitro without viral breakthrough. The derivatives, which contain...
Patients with inflammatory bowel disease (IBD) who experience long-term chronic inflammation of the colon are at an increased risk developing colorectal cancer (CRC). Mitotic spindle positioning (MISP), actin-binding protein, plays a role in mitosis and positioning. MISP is found on apical membrane intestinal mucosa helps stabilize elongate microvilli, offering protection against colitis. This study explored tumorigenesis using database, human CRC cells, mouse model for colitis-induced...
Immunological self-tolerance is established in the thymus by expression of virtually all self-antigens, including tissue-restricted antigens (TRAs) and cell-type-restricted (CRAs). Despite a wealth knowledge about transcriptional regulation TRA genes, posttranscriptional remains poorly understood. Here, we show that protein arginine methylation plays an essential role central immune tolerance maximizing self-antigen repertoire medullary thymic epithelial cells (mTECs). Protein...
Podocytes are terminally differentiated and highly specialized cells in the glomerulus, they form a crucial component of glomerular filtration barrier. The ICGN mouse is model dysfunction that shows gross morphological changes podocyte foot process, accompanied by proteinuria. Previously, we demonstrated proteinuria ICR-derived glomerulonephritis mice might be caused deletion mutation tensin2 (Tns2) gene (designated Tns2nph). To test whether this causes mutant phenotype, created knockout...
Desbuquois dysplasia (DD) type 1 is a rare skeletal characterized by short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium-activated nucleotidase (CANT1), which encodes that preferentially hydrolyzes UDP to UMP phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9-mediated genome editing. All F0 possessing frameshift deletions at both alleles exhibited dwarf phenotype. Germline transmission of the edited allele...
To identify factors involved in the earliest phase of differentiation human embryonic stem cells (hESCs) into brown adipocytes (BAs), we performed multi-time point microarray analyses. We found that growth/differentiation factor 15 (GDF15) expressions were specifically upregulated within three days differentiation, when immature hESC markers sustained. Although GDF15 continued to increase subsequent phases, GDF15-deficient hESCs differentiated mature BAs (Day 10) without apparent...
The Long-Evans Agouti (LEA/Tohm) rat has recently been established as a new model of type 2 diabetes. onset diabetes mellitus was observed only in male LEA/Tohm rats; however, urinary glucose appeared before the To clarify genetic basis glucose, we performed linkage analysis using (BN × LEA) F2 intercross progeny. A recessively acting locus responsible for excretion (ugl) mapped to 7.9 Mb region chromosome 10, which contains cystinosin (Ctns) gene. Ctns gene encodes cystine transporter,...
Most mitochondrial diseases are hereditary and highly heterogeneous. Cattle born with the V79L mutation in isoleucyl-tRNA synthetase 1 (IARS1) protein exhibit weak calf syndrome. Recent human genomic studies about pediatric also identified mutations IARS1 gene. Although severe prenatal-onset growth retardation infantile hepatopathy have been reported such patients, relationship between IARS symptoms is unknown. In this study, we generated hypomorphic IARS1V79L mutant mice to develop an...
SLC35A3 is considered an uridine diphosphate N- acetylglucosamine (UDP-GlcNAc) transporter in mammals and regulates the branching of N -glycans. A missense mutation causes complex vertebral malformation (CVM) cattle. However, biological functions have not been fully clarified. To address these issues, we established Slc35a3 –/– mice using CRISPR/Cas9 genome editing system. The generated mutant were perinatal lethal exhibited chondrodysplasia recapitulating CVM-like anomalies. During...
Tensin2 (TNS2) is a focal adhesion-localized protein possessing N-terminal tandem tyrosine phosphatase (PTPase) and C2 domains, C-terminal Src homology 2 (SH2) phosphotyrosine binding (PTB) domains. Genetic deletion of Tns2 in susceptible murine strain leads to podocyte alterations after birth. To clarify the domain contributions maintenance, we generated two Tns2-mutant mice with genetic background FVB/NJ strain, Tns2∆C Tns2CS mice, carrying SH2-PTB PTPase inactivation, respectively. The...