A5083134451- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Axon Guidance and Neuronal Signaling
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Renal Diseases and Glomerulopathies
- Caveolin-1 and cellular processes
- Proteoglycans and glycosaminoglycans research
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Erythrocyte Function and Pathophysiology
- Phytochemical and Pharmacological Studies
- Viral Infections and Immunology Research
- Blood groups and transfusion
- Complement system in diseases
- Flavonoids in Medical Research
- Hereditary Neurological Disorders
- Hematopoietic Stem Cell Transplantation
Kyoto University
2017-2025
Advanced Science Research Center
2007-2023
Kanazawa University
2005-2023
Central Institute for Experimental Animals
2021
Bone is remodeled constantly throughout life by bone-resorbing osteoclasts and bone-forming osteoblasts. To maintain bone volume quality, differentiation of osteoblasts tightly regulated through communication between within these two cell lineages. Previously we reported that cell-cell interaction mediated ephrinB2 ligand on EphB4 receptor generates bidirectional anti-osteoclastogenic pro-osteoblastogenic signals into respective cells presumably facilitates transition from resorption to...
Germline cells reprogramme extensive epigenetic modifications to ensure the cellular totipotency of subsequent generations and prevent accumulation epimutations. Notably, primordial germ (PGCs) erase genome-wide DNA methylation H3K9 dimethylation marks in a stepwise manner during migration gonadal periods. In this study, we profiled histone on transposable elements PGC development, examined role replication demethylation PGCs. CpGs short interspersed nuclear (SINEs) B1 B2 were substantially...
It is uncertain which β4-galactosyltransferase (β4GalT; gene name, B4galt), β4GalT-5 and/or β4GalT-6, responsible for the production of lactosylceramide (LacCer) synthase, functions in initial step ganglioside biosynthesis. Here, we generated conditional B4galt5 knockout (B4galt5 cKO) mice, using Nestin-Cre and crossed these with B4galt6 KO mice to generate 6 double (DKO) central nervous system (CNS). LacCer synthase activity major brain gangliosides were completely absent homogenates from...
During meiosis, specific histone modifications at pericentric heterochromatin (PCH), especially H3 tri- and dimethylation lysine 9 (H3K9me3 H3K9me2, respectively), are required for proper chromosome interactions. However, the molecular mechanism by which H3K9 methylation mediates synapsis is not yet understood. We have generated a Cbx3-deficient mouse line performed comparative analysis on Suv39h1/h2-, G9a- spermatocytes. This study revealed that H3K9me2 PCH depended Suv39h1/h2-mediated...
Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations SLC26A4 gene, encoding pendrin, causes non-syndromic with EVA or syndrome, a considerable number appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results loss. Here we identify EPHA2 as another causative gene syndrome SLC26A4. EphA2 forms protein complex controlling...
It was previously considered that protein knockdown using a combination of zinc finger degron tag and thalidomide analog is impossible in mouse cells, however, EGFP expression as an indicator, we found possible super-degron (SD) with iberdomide or mezigdomide cells. Despite the efficient degradation SD-tagged wild-type PD-1 could not be degraded but human Jurkat cells human-type CEREBLON (CRBNI391V). In mice CRBNI391V, endogenous tagged SD efficiently suppressed T both cultured whole body....
Glycosphingolipids (GSLs) are important for various biological functions in the nervous system, immune embryogenesis and other tissues processes. Lactosylceramide (LacCer), which is synthesized from glucosylceramide (GlcCer) by LacCer synthase, a core structure of GSLs, including gangliosides. synthase was reported to be β4-galactosyltransferase-6 (β4GalT-6) gene rat brain. However, existence another shown cultured cells lacking β4GalT-6. Here, we report that mainly β4GalT-5 during early...
Ephrin (Eph) signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and promote long-term potentiation. We investigated potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation a mouse model focal stroke. Cerebral ischemia was induced male C57Bl6/J wild-type (WT) EphA2-deficient (EphA2−/−) mice by middle cerebral artery occlusion (MCAO; 60 min), followed reperfusion (24 or 72 h). Brain infarction measured using...
Abstract Wilms' tumor 1‐associating protein (WTAP) was previously identified as a associated with tumor‐1 (WT‐1) that is essential for the development of genitourinary system. Although WTAP has been suggested to function in alternative splicing, stabilization mRNA, and cell growth, its vivo still unclear. We generated Wtap mutant mice using novel gene‐trap approach showed embryos exhibited defective egg‐cylinder formation at gastrulation stage died by embryonic day 10.5. they could form...
Signals from extraembryonic tissues in mice determine which proximal epiblast cells become primordial germ (PGCs). After their specification, approximately 40 PGCs appear at the base of allantoic bud and migrate to genital ridges, where they expand about 25 000 by Embryonic Day (E)13.5. The heterochromatin protein 1 (HP1) family members HP1alpha, HP1beta, HP1gamma (CBX5, CBX1, CBX3, respectively) are thought induce structure regulate gene expression binding methylated histone H3 lysine 9. We...
Abstract One of the physiologic consequences excessive UV radiation (UVR) exposure is apoptosis. This critical response serves to eliminate genetically injured cells and arises, in part, from activation DNA damage p53 signaling. Other contributory pathways, however, likely exist but have not been fully characterized. In a recent global screen UVR genes melanocytes, we identified receptor tyrosine kinase EPHA2. Using combination genetic pharmacologic approaches, set out investigate upstream...
Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that is essential differentiation various cell types, such as macrophages epidermal cells in mice, whereas involved cancer developmental diseases humans well Hox regulation zebrafish nematodes. Here, we report Jmjd3, but not Utx, axial skeletal formation mice. A mutant embryo (Jmjd3Δ18/Δ18), a catalytically inactive truncation (Utx-/y), showed anterior homeotic transformation. Quantitative RT-PCR...
Cbx3/HP1γ is a histone reader whose function in the immune system not completely understood. Here, we demonstrate that CD8+ T cells, insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type treated with there an increase of effector cells expressing stimulatory receptor Klrk1/NKG2D, decrease CD4+ CD25+ FOXP3+ regulatory (Treg cells) as well inhibitory CTLA4. Together these changes...
Mutations in the βMHC (β-myosin heavy chain), a sarcomeric protein are responsible for hypertrophic and dilated cardiomyopathy. However, mechanisms whereby distinct mutations gene cause two kinds of cardiomyopathy still unclear. In present study we report novel mutation found patient with isolated LVNC [LV (left ventricular) non-compaction] phenotype mouse mutant model carrying same mutation. To find responsible, searched genomic 99 unrelated probands five LVNC, identified p.Met531Arg...
Abstract Recently, targeted protein degradation systems have been developed using the ubiquitin-proteasome system. Here, we established Programmed cell death-1 (PD-1) knockdown mice as a model system for subjecting endogenous mouse proteins to small molecule-assisted shutoff (SMASh) degron SMASh degron-tagged PD-1-mCherry in Jurkat cells and CD3+ splenocytes were degraded by NS3/4A protease inhibitors, asunaprevir (ASV) or grazoprevir (GRV). Growth of MC-38 colon adenocarcinoma injected...
Abstract The role of carbohydrate chains in leukocyte migration to inflamed sites during inflammation and trafficking the lymph nodes under physiological conditions has been extensively characterized. Here, we report that also mediate homing engraftment hematopoietic stem/progenitor cells (HSPCs) bone marrow (BM). In particular, found transplanted BM deficient β-1,4-galactosyltransferase-1 (β4GalT-1) could not support survival mice exposed a lethal dose irradiation. obtained from β4GalT-1...
Background Beta-1,4-galactosyltransferase-3 (B4GALT3) belongs to the family of beta-1,4-galactosyltransferases (B4GALTs) and is responsible for transfer UDP-galactose terminal N -acetylglucosamine. B4GALT3 differentially expressed in tumors adjacent normal tissues, correlated with clinical prognosis several cancers, including neuroblastoma, cervical cancer, bladder cancer. However, exact role tumor immune microenvironment (TIME) remains unclear. Here, we aimed elucidate function TIME....
In vitro observations suggest a role for the mouse heterochromatin protein 1γ (HP-1γ) in immune system. However, it has not been shown if and how HP-1γ contributes to immunity vivo. Here we show that mice, positively regulates germinal center reaction high-affinity antibody response thymus (T)-dependent antigens by limiting size of CD8(+) regulatory T-cell (Treg) compartment without affecting progenitor B- or T-cell-development. Moreover, does control cell proliferation class switch...
Heterochromatin protein (HP) 1γ, a component of heterochromatin in eukaryotes, is involved H3K9 methylation. Although HP1γ expressed strongly neural tissues and stem cells, its functions are unclear. To elucidate the roles HP1γ, we analyzed -deficient (HP1γ KO) mouse embryonic neurospheres determined that KO tended to differentiate after quaternary culture. Several genes normally neuronal cells were upregulated undifferentiated neurospheres, but not wild type (WT). Compared control occupancy...
Patients benefit from drug therapy not only through pharmacological mechanisms, but also non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of brain. We consider that difference between responders and non-responders to placebo might related polymorphisms serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine lactose (placebo). Activity brain was...