- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Cancer-related Molecular Pathways
- Circadian rhythm and melatonin
- Ubiquitin and proteasome pathways
- Sleep and Wakefulness Research
- Photoacoustic and Ultrasonic Imaging
- Neuroinflammation and Neurodegeneration Mechanisms
- Optical Coherence Tomography Applications
- Neural dynamics and brain function
- Functional Brain Connectivity Studies
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Molecular Biology Techniques and Applications
- Light effects on plants
- Advanced biosensing and bioanalysis techniques
- Neurobiology and Insect Physiology Research
- Cell death mechanisms and regulation
- Cancer Research and Treatments
- Neonatal Respiratory Health Research
- Click Chemistry and Applications
- Neuroscience of respiration and sleep
- Chemical Synthesis and Analysis
- Advanced MRI Techniques and Applications
Juntendo University Hospital
2024-2025
The University of Tokyo
2014-2024
RIKEN Center for Biosystems Dynamics Research
2018-2024
Juntendo University
2020-2024
National Institutes for Quantum Science and Technology
2024
Nitto RIKEN (Japan)
2022
Japan Science and Technology Agency
2006-2019
Japan Agency for Medical Research and Development
2015-2016
Quantitative BioSciences
2015
RIKEN Center for Computational Science
2013
We describe a strategy for developing hydrophilic chemical cocktails tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive profiling. More than 1,600 chemicals were screened by high-throughput evaluation system each process. The profiling revealed important factors: salt-free amine with high octanol/water partition-coefficient (logP) N-alkylimidazole aromatic amide RI protonation of phosphate ion decalcification. strategic integration...
Abstract Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of system, we developed a highly optimized 3D pipeline based on CUBIC. Based our precise characterization biological tissues as an electrolyte gel, experimentally evaluated broad conditions by using artificial tissue-mimicking material. The combination allows bottom-up design superior protocol that can uniformly label whole...
Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because spatiotemporal expression profiles and dynamics neurotransmitter involved many functions delicately governed brain, vivo research tools with high resolution intact brains highly desirable. Covalent labeling by chemical reaction (chemical labeling) proteins without genetic manipulation is now a powerful method analyzing vitro. However, selective target receptor brain has not...
The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this method has some limitations in x-y axes due to its relatively narrow range observation area z-axis two-dimensionality. In study, we applied a CUBIC pipeline, which most powerful tissue-clearing three-dimensional (3D)-imaging technique, clinical pathology. was applicable 3D imaging both normal abnormal patient-derived,...
Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, also known as HIF stabilizers, increase endogenous erythropoietin production and serve novel therapeutic agents against anemia in chronic kidney disease. induces the expression of various genes related to energy metabolism an adaptive response hypoxia. However, it remains obscure how metabolic reprogramming renal tissue by stabilization affects pathophysiology diseases. Previous studies suggest that systemic disorders such...
Abstract Structural elucidation and molecular scrutiny of cerebral vasculature is crucial for understanding the functions diseases brain. Here, we introduce SeeNet, a method near-complete three-dimensional visualization vascular networks with high signal-to-noise ratios compatible phenotyping. SeeNet employs perfusion multifunctional crosslinker, casting by temperature-controlled polymerization hybrid hydrogels, bile salt-based tissue-clearing technique optimized observation connectivity....
Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM cleared specimens), low-cost ($20,000-50,000), low-expertise (one-day installation by non-expert), yet practical do-it-yourself microscope as solution this bottleneck. Even the most fundamental configuration enables multi-color imaging whole mouse brains and...
Under insulin-resistant conditions such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. A liver-brain-pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying compensatory β-cell proliferation. We identify FoxM1 activation islets from relay-stimulated mice. Blockade of relay, including vagotomy, inhibits obesity-induced pathway and suppresses expansion. Inducible β-cell-specific deficiency also blocks In...
Fluorescence imaging techniques have contributed to our understanding of various biological phenomenon; however, fluorescence spectral overlap significantly restricts multiplexing capability. Several strategies been reported overcome this limitation by utilizing the superior programmability DNA technologies and nanostructures, but in practice, it remains challenging achieve broad adoption these multiplexed detection methods due complexities designs. Here we report a color-changing...
Significance Statement The detailed role of neural activity in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study shows that activation β 2-adrenergic receptor (Adrb2) signaling macrophages induces expression T Ig mucin domain 3 ( Tim3 ), which contributes anti-inflammatory phenotypic alterations. Experiments using conditional knockout mice reveal macrophage Adrb2 directly mitigates LPS-induced systemic...
Fbxw7 (also known as Sel‐10, hCdc4 or hAgo) is the F‐box protein component of a Skp1–Cul1–F‐box (SCF) ubiquitin ligase. contributes to ubiquitin‐mediated degradation cyclin E, c‐Myc, Aurora‐A, Notch and c‐Jun, all which appear function cell‐cycle promoters oncogenic proteins. Loss results in elevated expression its substrates, may lead oncogenesis. However, it remains largely unclear accumulating substrate most related cancer development Fbxw7‐mutant cells. In present study, we examined...
The nuclear export and cytoplasmic degradation of the cyclin-dependent kinase inhibitor p27 are required for effective progression cell cycle through G(0)-G(1) transition. mechanism responsible this translocation has remained unclear, however. We now show that cyclin D2 directly links growth signaling with at transition in some types. up-regulation response to mitogenic stimulation was found occur earlier than other D-type cyclins parallel down-regulation RNA interference-mediated depletion...
Although p27 and p57 are structurally related cyclin-dependent kinase inhibitors (CKIs), thought to perform similar functions, knockout (p27 KO ) mice show distinct phenotypes. To elucidate the in vivo functions of these CKIs, we have now generated a knock-in mouse model (p57 p27KI ), which gene has been replaced with gene. The viable appear healthy, most developmental defects characteristic having corrected by knock-in. Such were also ameliorated deficient both transcription factor E2F1,...
Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as kidney. Here, we establish combinations genetic immuno-labelling single cell identification, subsequent de-clarification histoimmunopathology transmission electron microscopy. Using advanced light microscopy computational analyses, investigated a murine model crescentic nephritis, an inflammatory kidney disease...