A5019032651- Allergic Rhinitis and Sensitization
- Immune cells in cancer
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Mast cells and histamine
- Dermatology and Skin Diseases
- Extracellular vesicles in disease
- Craniofacial Disorders and Treatments
- RNA Research and Splicing
- Asthma and respiratory diseases
- Receptor Mechanisms and Signaling
- Cardiac Fibrosis and Remodeling
- Coronary Artery Anomalies
- Cell Image Analysis Techniques
- Food Allergy and Anaphylaxis Research
- Immune Response and Inflammation
- Birth, Development, and Health
- Cardiomyopathy and Myosin Studies
- Chemokine receptors and signaling
- Dermatological diseases and infestations
- Phagocytosis and Immune Regulation
- Molecular Biology Techniques and Applications
- Cardiac electrophysiology and arrhythmias
- Chemical Synthesis and Analysis
Wellcome Sanger Institute
2022-2025
University of Tsukuba
2013-2021
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
2018
Japan Science and Technology Agency
2013
Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized transcriptome 880,000 nuclei from 18 control 61 failing, nonischemic human hearts with pathogenic DCM ACM or idiopathic disease. We performed genotype-stratified analyses ventricular cell lineages transcriptional states. The resultant atlas demonstrated distinct...
The function of a cell is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here we combine single-cell spatial transcriptomics data to discover cellular niches within eight regions human heart. We map cells microanatomical locations integrate knowledge-based unsupervised structural annotations. also profile cardiac conduction system
Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes key regulatory factors that underlie lineage commitment these cells remain elusive. Here we applied paired transcriptional profiling approximately 336,000 nucleus droplets spatial transcriptomics to establish a multi-omic atlas human cranium development between 5 11 weeks after conception. Using combined modelling data,...
Abstract Developmental dynamics encompass both the specification of cell types and their spatial organisation into multicellular niches. Here we harness power single-cell multiomics to unravel embryonic foetal cardiac tissue niches, which lead development a new tool, TissueTypist. We reveal that cardiac-resident macrophages likely originate from yolk sac, forming heterogeneous subsets. CX3CR1 + with microglia-like profile localise in sinoatrial node, may contribute axon guidance for...
Abstract Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive and active fetal are not known. In this study, we combined hearts using single-cell single-nuclei RNA sequencing compared epicardial cells from both stages. We found that migratory fibroblast-like population only in heart expressed angiogenic gene programs, whereas was solely mesothelial immune responsive....
Immune responses contribute to tissue injury and repair during after ischemic stroke. However, the spatiotemporal initiating molecular events remain incompletely understood. Here, we show that mice deficient in phosphatidylserine receptor CD300a, which is highly expressed on brain myeloid cells including Ly6Chi monocytes, exhibited ameliorated neurological deficit middle cerebral artery occlusion (MCAO). CD300a inhibited signaling through CD300b-DNAX-activation protein 12 (DAP12) pathway...
Significance Immune tolerance is essential to prevent autoimmune responses, but it often needs be limited for proper immune response. Regulatory T (Treg) cells play a crucial role in tolerance; however, their immune-suppressive function restricted under inflammatory conditions. Here, we show that the activated receptor DNAM-1 limits Treg cell regardless of DNAM-1–mediated intracellular signaling. We found competes with immunoreceptor Ig and ITIM domains (TIGIT) binding common ligand....
Abstract The human heart and adjoining great vessels consist of multiple cell types vital for life, yet many remain uncharacterised molecularly during development. Here, we performed a high-resolution profiling the first second trimesters, defining 63 with distinct identity location-specific signatures. We reveal previously unreported types, including pericardium ductus arteriosus. At ventricles, identified signatures involved in establishing trabeculation-compaction right-left axes...
Clec10a on skin macrophages recognizes a mucin-like molecule of house dust mite and suppresses mite-induced dermatitis.
Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated microenvironments remains unclear. Here, we found that mice deficient the inhibitory immunoreceptor CD300a on their dendritic (DCs) have increased numbers of tumors and greater growth compared with wild-type after transplantation B16 melanoma. Pharmacological impairment extracellular vesicle (EV) release decreased CD300a-deficient mice. Coculture DCs...
The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around third ventricle give rise to various several hypothalamic nuclei. show conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities sex-biased behaviors reproductive organs both sexes. Gonadal hormone administration...
Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient MAIR-II (also called CLM-4 or LMIR2) more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer inflammatory from WT mice, but MAIR-II, TLR4 MyD88-deficient significantly improves survival MAIR-II-deficient after...
Abstract A cell’s function is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here, we combine single-cell spatial transcriptomic data to discover cellular niches within eight regions of human heart. We map cells micro-anatomic locations integrate knowledge-based unsupervised structural annotations. For first time, profile cardiac conduction system, revealing their distinctive repertoire ion channels, G-protein coupled receptors, cell...
Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both mouse MC. Although suppresses IgE-mediated, mast cell–dependent anaphylaxis mice, the expression profile function primary remains undetermined. Here, we established a seven-color flow cytometry method for assessing very small number We show that Allergin-1S1, splicing...
House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in cell development HDM-induced asthma. However, the regulatory mechanism DC activation remains incompletely understood. In this study, we demonstrate that mice deficient an inhibitory immunoreceptor, Allergin-1, showed exacerbated airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric were sensitized with...
Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various have been identified, the regulatory mechanism of is not fully understood. To understand mechanisms activation, we used gene expression analyses human mouse identify a novel immunoreceptor MCs. We found that Tek, which encodes Tie2, was preferentially both humans mice. However, Tie2...
ABSTRACT POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due part to its cAMP-dependent binding regulation of TREK-1 potassium channels. Loss Popdc2 mice results sinus pauses bradycardia morpholino knockdown popdc2 zebrafish atrioventricular (AV) block. We identified bi-allelic variants 4 families that presented with a phenotypic spectrum consisting node dysfunction, AV conduction defects hypertrophic cardiomyopathy....
Abstract Bone and joint formation in the developing skeleton rely on co-ordinated differentiation of progenitors nascent limbs joints. The cell states, epigenetic processes key regulatory factors underlying their lineage commitment to osteogenic other mesenchymal populations during ossification remain poorly understood are largely unexplored human studies. Here, we apply paired single-nuclei transcriptional profiling 336,000 droplets, addition spatial transcriptomics, construct a...
DNAM-1 is an activating immunoreceptor on T cells and natural killer (NK) cells. Expression levels of its ligands, CD155 CD112, are up-regulated tumor The interaction CD8+ NK with the ligands plays important role in immunity. We previously reported that mice deficient showed accelerated growth tumors induced by chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Contrary to those results, we show here development 12-O-tetradecanoylphorbol-13-acetate (TPA) together DMBA was suppressed...