Featured Publications
Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases
Yasumizu Y, Takeuchi D, Morimoto R, Takeshima Y, Okuno T, Kinoshita M, Morita T, Kato Y, Wang M, Motooka D, Okuzaki D, Nakamura Y, Mikami N, Arai M, Zhang X, Kumanogoh A, Mochizuki H, Ohkura N, Sakaguchi S. Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases. Cell Genomics 2024, 4: 100473. PMID: 38359792, PMCID: PMC10879034, DOI: 10.1016/j.xgen.2023.100473.Peer-Reviewed Original ResearchConceptsGene programSingle-cell transcriptomic landscapeSingle-cell datasetsCell subpopulationsTranscriptional programsTranscriptomic characterizationCD4<sup>+</sup> T-cell subpopulationsCD4<sup>+</sup> T cellsCellular heterogeneityT cell subpopulationsAutoimmune diseasesCell heterogeneityT cellsPeripheral CD4<sup>+</sup> T cellsCell populationsCD4+ T cell populationCanonical clustersCellsT cell populationsQualitative alterationsT cell heterogeneityGenesSubpopulationsClinical statusCell frequencyMyasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma
Yasumizu Y, Ohkura N, Murata H, Kinoshita M, Funaki S, Nojima S, Kido K, Kohara M, Motooka D, Okuzaki D, Suganami S, Takeuchi E, Nakamura Y, Takeshima Y, Arai M, Tada S, Okumura M, Morii E, Shintani Y, Sakaguchi S, Okuno T, Mochizuki H. Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma. Nature Communications 2022, 13: 4230. PMID: 35869073, PMCID: PMC9305039, DOI: 10.1038/s41467-022-31951-8.Peer-Reviewed Original ResearchConceptsMedullary thymic epithelial cellsEctopic expressionCellular composition estimationSingle-cell RNA sequencingThymic epithelial cellsSubpopulation of medullary thymic epithelial cellsEpithelial cellsMG-thymomaRNA sequencingGene expressionCell-cell interaction analysisCell migrationComprehensive atlasEctopic germinal center formationInteraction analysisDendritic cell migrationGerminal center formationMyasthenia gravisCellsTranscriptomeCXCL12-CXCR4Cell accumulationT/B cellsVIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data
Yasumizu Y, Hara A, Sakaguchi S, Ohkura N. VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data. Bioinformatics 2020, 37: 1465-1467. PMID: 33017003, PMCID: PMC7745649, DOI: 10.1093/bioinformatics/btaa859.Peer-Reviewed Original ResearchConceptsConventional RNA-seq dataRNA-seq dataSequence dataSupplementary dataRNA transcriptsBioinformatics methodsVirus copy numberRNA sequencingCopy numberVirus RNAHuman cellsExpression profilesBioinformaticsMultiple virusesInfected cellsClinical samplesTranscriptionRNACellsVirusVirus analysisSARS-CoV-2SequenceMRNAHerpesvirusRegulatory T Cell-Specific Epigenomic Region Variants Are a Key Determinant of Susceptibility to Common Autoimmune Diseases
Ohkura N, Yasumizu Y, Kitagawa Y, Tanaka A, Nakamura Y, Motooka D, Nakamura S, Okada Y, Sakaguchi S. Regulatory T Cell-Specific Epigenomic Region Variants Are a Key Determinant of Susceptibility to Common Autoimmune Diseases. Immunity 2020, 52: 1119-1132.e4. PMID: 32362325, DOI: 10.1016/j.immuni.2020.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune DiseasesBiomarkersCell DifferentiationComputational BiologyCpG IslandsDNA MethylationEpigenesis, GeneticEpigenomicsGene Expression ProfilingGenetic Predisposition to DiseaseGenetic VariationHumansImmunophenotypingPolymorphism, Single NucleotideT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscriptomeConceptsCommon autoimmune diseasesSingle-nucleotide polymorphismsSusceptibility to common autoimmune diseasesCell-specific gene transcriptionGenome-wide epigenetic profilingAssociated with common autoimmune diseasesAssociated with transcriptionPolygenic autoimmune diseasesTreg cellsDemethylated regionCpG hypomethylationSuper-enhancersAutoimmune diseasesDeterminants of susceptibilityEpigenetic modificationsEpigenetic profilesGene transcriptionEpigenetic changesTreg-cell-specific demethylated regionNaive Treg cellsNatural Treg cellsRegional variantsTranscriptionActive stateCellsGenome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population
Yasumizu Y, Sakaue S, Konuma T, Suzuki K, Matsuda K, Murakami Y, Kubo M, Palamara P, Kamatani Y, Okada Y. Genome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population. Molecular Biology And Evolution 2020, 37: 1306-1316. PMID: 31957793, PMCID: PMC7182208, DOI: 10.1093/molbev/msaa005.Peer-Reviewed Original ResearchConceptsSelection signaturesNatural selection signaturesTrait-associated variantsGenome-wide scanGenome-wide significanceAlcohol dehydrogenaseNatural selection studyPopulation-specific featuresAlcohol-related phenotypesAdaptive evolutionFine-mappingGenetic lociCluster locusUK Biobank ResourcePhenotypic dataHuman phenotypesSelection pressureJapanese populationEnrichment analysisPopulation-specific evidencePhenotypic spectrumPhenotypeBiobank ResourceGenetic riskImmune-related diseases
2024
A newly identified gene Ahed plays essential roles in murine haematopoiesis
Nakai R, Yokota T, Tokunaga M, Takaishi M, Yokomizo T, Sudo T, Shi H, Yasumizu Y, Okuzaki D, Kokubu C, Tanaka S, Takaoka K, Yamanishi A, Yoshida J, Watanabe H, Kondoh G, Horie K, Hosen N, Sano S, Takeda J. A newly identified gene Ahed plays essential roles in murine haematopoiesis. Nature Communications 2024, 15: 5090. PMID: 38918373, PMCID: PMC11199565, DOI: 10.1038/s41467-024-49252-7.Peer-Reviewed Original ResearchConceptsMutant embryonic stem cellsConditional knockoutUncharacterised genesHaematopoietic cellsNuclear proteinsFunctional genesHaematopoiesis in vivoAssociated with malignancyBiological functionsGenesSomatic mutationsEmbryonic stem cellsHaematopoietic developmentTransplantation experimentsHaematological malignanciesDeletionAdult miceCancer patientsCoordinated actionEmbryonic dayStem cellsHaematopoiesisMurine haematopoiesisCellsMalignancy
2023
Increased anti‐oxidative action compensates for collagen tissue degeneration in vitiligo dermis
Yokoi K, Yasumizu Y, Ohkura N, Shinzawa K, Okuzaki D, Shimoda N, Ando H, Yamada N, Fujimoto M, Tanemura A. Increased anti‐oxidative action compensates for collagen tissue degeneration in vitiligo dermis. Pigment Cell & Melanoma Research 2023, 36: 355-364. PMID: 37230937, DOI: 10.1111/pcmr.13094.Peer-Reviewed Original ResearchConceptsCollagen-related genesUninvolved perilesional skinOxidative stressSignaling pathway activationCollagen homeostasisVitiligo lesionsPathway activationPerilesional skinExpression levelsAnti-oxidant enzymesAnti-oxidative actionDegraded collagen fibersNrf2 signaling pathway activationDefense systemProduction of oxidative stress
2022
Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder
Murata H, Kinoshita M, Yasumizu Y, Motooka D, Beppu S, Shiraishi N, Sugiyama Y, Kihara K, Tada S, Koda T, Konaka H, Takamatsu H, Kumanogoh A, Okuno T, Mochizuki H. Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1149. PMID: 35210295, PMCID: PMC8874356, DOI: 10.1212/nxi.0000000000001149.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderPeripheral blood mononuclear cellsCell-free DNAAquaporin-4 antibody-positive neuromyelitis optica spectrum disorderAntibody-positive neuromyelitis optica spectrum disorderPathogenesis of neuromyelitis optica spectrum disordersToll-like receptor 9 antagonistIFN-1IFN-1 pathwayInhibition of NETosisPeripheral immune systemOrigin of cell-free DNABlood mononuclear cellsPredominant cellular sourceIFN-1 productionType 1 interferonLL37 antimicrobial peptideWhole blood transcriptome analysisAquaporin-4Mononuclear cellsCfDNA fractionDNA methylation profilesBlood transcriptome analysisHealthy subjectsCellular sourceCCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory
Kidani Y, Nogami W, Yasumizu Y, Kawashima A, Tanaka A, Sonoda Y, Tona Y, Nashiki K, Matsumoto R, Hagiwara M, Osaki M, Dohi K, Kanazawa T, Ueyama A, Yoshikawa M, Yoshida T, Matsumoto M, Hojo K, Shinonome S, Yoshida H, Hirata M, Haruna M, Nakamura Y, Motooka D, Okuzaki D, Sugiyama Y, Kinoshita M, Okuno T, Kato T, Hatano K, Uemura M, Imamura R, Yokoi K, Tanemura A, Shintani Y, Kimura T, Nonomura N, Wada H, Mori M, Doki Y, Ohkura N, Sakaguchi S. CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2114282119. PMID: 35140181, PMCID: PMC8851483, DOI: 10.1073/pnas.2114282119.Peer-Reviewed Original ResearchConceptsTumor TregsTumor immunityMAb treatmentTumor tissuesT cellsLong-lasting memoryCD4<sup>+</sup> regulatory T cellsPD-1 immune checkpoint blockadeCures of established tumorsInduce severe autoimmune diseaseSuppress antitumor immune responsesImmune responseT cell receptor clonotypesImmune checkpoint blockadeSystemic Treg depletionAntitumor immune responseConventional T cellsRegulatory T cellsTumor-associated antigensChemokine receptor CCR8Several autoimmune diseasesSecondary immune responseTreg depletionCheckpoint blockadePD-1piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis
Abdelhamid R, Ogawa K, Beck G, Ikenaka K, Takeuchi E, Yasumizu Y, Jinno J, Kimura Y, Baba K, Nagai Y, Okada Y, Saito Y, Murayama S, Mochizuki H, Nagano S. piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis. Molecular Neurobiology 2022, 59: 1693-1705. PMID: 35015250, PMCID: PMC8882100, DOI: 10.1007/s12035-021-02686-2.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsNon-coding RNAsBind to PIWI-interacting RNAsDysregulation of piRNAsControl postmortem brain samplesAmyotrophic lateral sclerosisTDP-43Biogenesis of RNAsAggregation of TAR DNA-binding protein 43RNA-binding proteinsTAR DNA-binding protein 43DNA-binding protein 43Abnormal RNA metabolismNcRNA biogenesisPIWI proteinsPiwi homologsSilencing 1Sporadic ALSRNA metabolismRNA-seqTDP-43 pathologyProtein complexesPIWIL1Sporadic amyotrophic lateral sclerosisPathological hallmarkHigh cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD)
Beppu S, Kinoshita M, Wilamowski J, Suenaga T, Yasumizu Y, Ogawa K, Ishikura T, Tada S, Koda T, Murata H, Shiraishi N, Sugiyama Y, Kihara K, Sugimoto T, Arase H, Standley D, Okuno T, Mochizuki H. High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD). Scientific Reports 2022, 12: 106. PMID: 34997058, PMCID: PMC8742014, DOI: 10.1038/s41598-021-04074-1.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderPeptide major histocompatibility complexDevelopment of neuromyelitis optica spectrum disorderAnti-aquaporin-4HLA-DQA1Associated with neuromyelitis optica spectrum disordersHigh cell surface expressionJapanese patient cohortPresence of pathogenic autoantibodiesCell surface expression levelsRelapsing autoimmune diseaseHLA-DQA1 allelesCell surface expressionSurface expression levelsAQP4 peptidesMajor histocompatibility complexAnti-aquaporinPathogenic autoantibodiesHLA-DQPatient cohortAutoimmune diseasesPathogenic roleSurface expressionIn silico 3D structure modelingHistocompatibility complex
2021
Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
Harada A, Matsumoto S, Yasumizu Y, Shojima K, Akama T, Eguchi H, Kikuchi A. Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion. ELife 2021, 10: e66721. PMID: 34590580, PMCID: PMC8598236, DOI: 10.7554/elife.66721.Peer-Reviewed Original ResearchConceptsDownstream effectorsEGF-Ras pathwayCancer cell invasionPancreatic cancer patientsPancreatic cancer cellsIQGAP1ARL4CCell invasionPancreatic cancerSite of invasionCancer cellsCancer patientsExtracellular matrixPseudopodsAntisense oligonucleotidesInvasive pancreatic cancerMetastasis of pancreatic cancerActive siteInduced degradationEffectorMMP14InvasionMortality rateLocalizationOligonucleotidesAnti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats
Ishikura T, Kinoshita M, Shimizu M, Yasumizu Y, Motooka D, Okuzaki D, Yamashita K, Murata H, Beppu S, Koda T, Tada S, Shiraishi N, Sugiyama Y, Miyamoto K, Kusunoki S, Sugimoto T, Kumanogoh A, Okuno T, Mochizuki H. Anti-AQP4 autoantibodies promote ATP release from astrocytes and induce mechanical pain in rats. Journal Of Neuroinflammation 2021, 18: 181. PMID: 34419102, PMCID: PMC8380350, DOI: 10.1186/s12974-021-02232-w.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderIgG-treated ratsMechanical allodyniaNeuropathic painSpinal cordATP receptorsATP releaseSymptoms of neuromyelitis optica spectrum disorderDevelopment of mechanical allodyniaDevelopment of neuropathic painPharmacological inhibitionDevelopment of painful symptomsAnti-AQP4 autoantibodiesPeripheral neuropathic painAnti-AQP4 antibodyRelease of extracellular ATPExtracellular ATP releaseRat spinal cordDamage-associated molecular patternsAnti-AQP4Pain mechanismsMechanical painInvolvement of ATPPain symptomsRemission phaseFull-length 16S rRNA gene amplicon analysis of human gut microbiota using MinION™ nanopore sequencing confers species-level resolution
Matsuo Y, Komiya S, Yasumizu Y, Yasuoka Y, Mizushima K, Takagi T, Kryukov K, Fukuda A, Morimoto Y, Naito Y, Okada H, Bono H, Nakagawa S, Hirota K. Full-length 16S rRNA gene amplicon analysis of human gut microbiota using MinION™ nanopore sequencing confers species-level resolution. BMC Microbiology 2021, 21: 35. PMID: 33499799, PMCID: PMC7836573, DOI: 10.1186/s12866-021-02094-5.Peer-Reviewed Original ResearchConceptsRRNA gene amplicon sequencingShort-read sequencingHuman gut microbiotaGene amplicon sequencingAmplicon sequencingRibosomal RNAGut microbiotaTaxonomic classificationBacterial communitiesBacterial compositionFull-length 16S rRNA geneShort-read sequencing methodsConventional short-read sequencing methodsDominant bacterial generaMock bacterial communityLong-read sequencingTaxonomic classification of bacteriaComplex bacterial communitiesRRNA gene analysisClassification of bacteriaComplex bacterial compositionHuman fecal samplesRRNA geneNanopore sequencingMicrobiome studies
2020
Proenkephalin+ regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function
Shime H, Odanaka M, Tsuiji M, Matoba T, Imai M, Yasumizu Y, Uraki R, Minohara K, Watanabe M, Bonito A, Fukuyama H, Ohkura N, Sakaguchi S, Morita A, Yamazaki S. Proenkephalin+ regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20696-20705. PMID: 32769209, PMCID: PMC7456133, DOI: 10.1073/pnas.2000372117.Peer-Reviewed Original ResearchConceptsTreg cellsUltraviolet B exposureUnique TCR repertoireFoxp3 transcription factorRegulatory T cellsSkin homeostasisSkin explant assayImmunological self-toleranceFunctional regulatory TUltraviolet BWound healingSuppress various immune responsesEndogenous opioid precursorsSkin TregsExpressed CD25Regulatory TTCR repertoireProenkephalin expressionT cellsSelf-toleranceWound closure assayImmune responseTregsInflammatory responseMet-Enk
2018
Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn’s Disease Patients
Sekido Y, Yasumizu Y, Nishimura J, Kayama H, Matsuno H, Ogino T, Miyoshi N, Takahashi H, Haraguchi N, Hata T, Matsuda C, Doki Y, Mori M, Takeda K, Ohkura N, Sakaguchi S, Mizushima T. Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn’s Disease Patients. Digestion 2018, 99: 194-204. PMID: 30343293, DOI: 10.1159/000490890.Peer-Reviewed Original ResearchConceptsGene expression patternsGO BP termsExpression patternsGene OntologyGut homeostasisMyeloid cell subsetsInnate myeloid cellsBiological processesCrohn's diseaseComprehensive gene expression profilesMaintenance of gut homeostasisCell type-specific mechanismsCell subsetsMyeloid cellsHuman colonGene expression profilesHuman intestinal lamina propriaInnate immune responseLamina propriaType-specific mechanismsTranscriptional analysisGO-BPRNA sequencingDisease patientsPathogenesis of Crohn's disease