2025
An international perspective on the future of systemic sclerosis research
Abraham D, Black C, Denton C, Distler J, Domsic R, Feghali-Bostwick C, Gourh P, Hinchcliff M, Kolling F, Kuwana M, Lafyatis R, Landegren U, Mahoney J, Martin J, Matucci-Cerinic M, McMahan Z, Mora A, Mouthon L, Rabinovitch M, Rojas M, Rubin K, Trojanowska M, Varga J, Whitfield M, Gabrielli A, Krieg T. An international perspective on the future of systemic sclerosis research. Nature Reviews Rheumatology 2025, 21: 174-187. PMID: 39953141, DOI: 10.1038/s41584-024-01217-2.Peer-Reviewed Original ResearchConceptsSystemic sclerosisSystemic sclerosis researchHistory of systemic sclerosisInnovative clinical trial designsSystemic autoimmune diseaseEarly pathogenetic eventClinical trial designCollaborative global effortAutoimmune phenomenaImprove patient outcomesDisease activityMicrovascular dysfunctionClinical historyEmergency therapyAutoimmune diseasesDisease-modifying treatmentsTissue fibrosisSingle-cell RNA sequencingClinical heterogeneityEffective disease-modifying treatmentsPersonalized therapyAnimal modelsComplex pathogenesisEffective treatmentNext-generation sequencingThe Dyson equalizer: adaptive noise stabilization for low-rank signal detection and recovery
Landa B, Kluger Y. The Dyson equalizer: adaptive noise stabilization for low-rank signal detection and recovery. Information And Inference A Journal Of The IMA 2025, 14: iaae036. PMID: 39830802, PMCID: PMC11735832, DOI: 10.1093/imaiai/iaae036.Peer-Reviewed Original ResearchNoise varianceLow-rank signalData matrixNoisy data matrixSignal detectionImproved signal recoverySignal recoveryMP lawNoise distributionRandom matrix theory resultsSignal structureData-drivenSingular valuesNoiseDataTaskNoise characteristicsNoise levelNoise stabilitySingle-cell RNA sequencingDetectionSpatial transcriptomics dataTranscriptome dataNormalization procedureMatrix
2024
Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact
Albertson A, Winkler E, Yang A, Buckwalter M, Dingman A, Fan H, Herson P, McCullough L, Perez-Pinzon M, Sansing L, Sun D, Alkayed N. Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact. Stroke 2024, 56: 1082-1091. PMID: 39772596, DOI: 10.1161/strokeaha.124.049001.Peer-Reviewed Original ResearchInterplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity
Furtado J, Geraldo L, Leser F, Bartkowiak B, Poulet M, Park H, Robinson M, Pibouin-Fragner L, Eichmann A, Boyé K. Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408674121. PMID: 39693351, PMCID: PMC11670198, DOI: 10.1073/pnas.2408674121.Peer-Reviewed Original ResearchConceptsBlood-retina barrierBlood-retina barrier integrityGene expressionScRNA-seqEndothelial cellsNetrin-1 receptor UNC5BNetrin-1Cell gene expression programsSingle-cell RNA sequencingDevelopment of retinal diseasesWnt signaling componentsGene expression programsTight junction proteinsMutant endothelial cellsScaffold proteinTranscriptional activityLoss of functionRNA sequencingRetinal arteriolesRetina endothelial cellsRetinal diseasesHomologue 1Expression programsReceptor UNC5BEndothelial subtypesSDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
Liu Y, Li N, Qi J, Xu G, Zhao J, Wang N, Huang X, Jiang W, Wei H, Justet A, Adams T, Homer R, Amei A, Rosas I, Kaminski N, Wang Z, Yan X. SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data. Genome Biology 2024, 25: 271. PMID: 39402626, PMCID: PMC11475911, DOI: 10.1186/s13059-024-03416-2.Peer-Reviewed Original ResearchShear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques
Zhou Z, Korteland S, Tardajos-Ayllon B, Wu J, Chambers E, Weninck J, Simons M, Dunning M, Schenkel T, Diagbouga M, Wentzel J, Fragiadaki M, Evans P. Shear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques. Atherosclerosis 2024, 398: 118622. PMID: 39413592, DOI: 10.1016/j.atherosclerosis.2024.118622.Peer-Reviewed Original ResearchConceptsShear stressPhysiological shear stressComputational fluid dynamicsDiseased arteriesHealthy arteriesGene Ontology termsFluid dynamicsSingle-cell RNA sequencingApoptotic gene expressionEffect of physiological shear stressPromote vascular homeostasisOntology termsRNA sequencingFunctional enrichmentEndothelial cellsGene expressionRisk of cardiovascular complicationsCross-tissue organization of myeloid cells in scleroderma and related fibrotic diseases
Odell I. Cross-tissue organization of myeloid cells in scleroderma and related fibrotic diseases. Current Opinion In Rheumatology 2024, 36: 379-386. PMID: 39171604, PMCID: PMC11451931, DOI: 10.1097/bor.0000000000001047.Peer-Reviewed Original ResearchScRNA-seqIdiopathic pulmonary fibrosisMyeloid cell typesScRNA-seq studiesScRNA-seq analysisSingle-cell RNA sequencingCell typesDendritic cellsFc receptor genesScleroderma skinExpression of EREGLung fibrosis severityFibrotic diseasesMyeloid cell populationsRNA sequencingMultiple tissuesSignaling mechanismsReceptor geneMyeloid cellsSSc skinPulmonary fibrosisFibrosis severityLung fibrosisCardiac fibrosisSPP1Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection
Yang L, Han Y, Zhang T, Dong X, Ge J, Roy A, Zhu J, Lu T, Vandana J, de Silva N, Robertson C, Xiang J, Pan C, Sun Y, Que J, Evans T, Liu C, Wang W, Naji A, Parker S, Schwartz R, Chen S. Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection. Cell Stem Cell 2024, 31: 1612-1629.e8. PMID: 39232561, PMCID: PMC11546835, DOI: 10.1016/j.stem.2024.08.007.Peer-Reviewed Original ResearchProinflammatory macrophagesActivation of proinflammatory macrophagesImmune cell changesCoxsackievirus B4Host damageAccumulation of proinflammatory macrophagesSingle-cell RNA sequencingMulti-omics platformsB cellsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Marker expressionViral infectionViral exposureSyndrome coronavirus 2Endothelial cellsCell changesRNA sequencingSARS-CoV-2MacrophagesCell damageAutopsy samplesOrganoidsPyroptosisSingle-cell RNA sequencing reveals melanoma cell state-dependent heterogeneity of response to MAPK inhibitors
Lim S, Lin Y, Lee J, Pedersen B, Stewart A, Scolyer R, Long G, Yang J, Rizos H. Single-cell RNA sequencing reveals melanoma cell state-dependent heterogeneity of response to MAPK inhibitors. EBioMedicine 2024, 107: 105308. PMID: 39216232, PMCID: PMC11402938, DOI: 10.1016/j.ebiom.2024.105308.Peer-Reviewed Original ResearchMelanoma cellsTranscriptional cell statesTreatment responseSingle-cell RNA sequencingResponse to MAPK inhibitorsPlasticity of melanoma cellsBRAF/MEK inhibitor treatmentImmunotherapy-resistant tumorsMelanoma Institute AustraliaNational Health and Medical Research Council of AustraliaImpact treatment responseMelanoma cell statesPro-inflammatory signalingNational Health and Medical Research CouncilCell statesPro-inflammatory IL6Melanoma tumorsHeterogeneous cancerInhibitor resistanceInhibitor treatmentMelanomaBRAF/MEKRNA sequencingMAPK inhibitorStudy treatment responsesPlasma proteomics of acute tubular injury
Schmidt I, Surapaneni A, Zhao R, Upadhyay D, Yeo W, Schlosser P, Huynh C, Srivastava A, Palsson R, Kim T, Stillman I, Barwinska D, Barasch J, Eadon M, El-Achkar T, Henderson J, Moledina D, Rosas S, Claudel S, Verma A, Wen Y, Lindenmayer M, Huber T, Parikh S, Shapiro J, Rovin B, Stanaway I, Sathe N, Bhatraju P, Coresh J, Rhee E, Grams M, Waikar S. Plasma proteomics of acute tubular injury. Nature Communications 2024, 15: 7368. PMID: 39191768, PMCID: PMC11349760, DOI: 10.1038/s41467-024-51304-x.Peer-Reviewed Original ResearchConceptsAcute tubular injuryAcute kidney injuryPathway analysisOrganelle stress responsesSingle-cell RNA sequencingKidney Precision Medicine ProjectKidney diseaseSOMAscan proteomics platformProgression to kidney failureRNA sequencingBiological pathwaysGene expressionStress responseNon-invasive biomarkersProteomics platformMannose receptor 1Kidney injuryTubular injuryImmune regulationReceptor 1Macrophage mannose receptor 1Host responseBiomarker proteinsPrecision Medicine ProjectKidney failureSingle-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantTWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn’s disease
Zhang Y, Wang J, Sun H, Xun Z, He Z, Zhao Y, Qi J, Sun S, Yang Q, Gu Y, Zhang L, Zhou C, Ye Y, Wu N, Zou D, Su B. TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn’s disease. Journal Of Clinical Investigation 2024, 134: e179472. PMID: 39024569, PMCID: PMC11405050, DOI: 10.1172/jci179472.Peer-Reviewed Original ResearchExcessive extracellular matrixComplication of Crohn's diseaseDextran sulfate sodium saltSingle-cell RNA sequencingMesenchymal stromal cellsTGF-b signalingScRNA-seqCrohn's diseaseIntestinal fibrosisCell transcriptomic profilingRNA sequencingTranscriptome profilingSingle cell transcriptomic profilingInhibition of Twist1Murine colitis modelPathogenesis of intestinal fibrosisAnti-fibrosis drugsExtracellular matrixPharmacological inhibitionFibrotic intestineFibrotic sitesTwist1 expressionECM productionCD patientsIntestinal obstructionBACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Thakore P, Schnell A, Huang L, Zhao M, Hou Y, Christian E, Zaghouani S, Wang C, Singh V, Singaraju A, Krishnan R, Kozoriz D, Ma S, Sankar V, Notarbartolo S, Buenrostro J, Sallusto F, Patsopoulos N, Rozenblatt-Rosen O, Kuchroo V, Regev A. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells. Nature Immunology 2024, 25: 1395-1410. PMID: 39009838, DOI: 10.1038/s41590-024-01901-1.Peer-Reviewed Original ResearchConceptsTransposase-accessible chromatin sequencingSingle-cell RNA sequencingTh17 heterogeneitySingle-cell assaysScATAC-seqChromatin landscapeChromatin stateChromatin sequencingRegulatory networksScRNA-seqTh17 cell pathogenicityHuman geneticsIn vivoRNA sequencingChromatin configurationRegulatory pathwaysTissue homeostasisCell statesCells in vitroBach2ChromatinSequenceCellsType 1 helper T (Th1) cellsCD4+ T cell subsetsZika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut
Chen T, Raduwan H, Marín-López A, Cui Y, Fikrig E. Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut. IScience 2024, 27: 110353. PMID: 39055935, PMCID: PMC11269924, DOI: 10.1016/j.isci.2024.110353.Peer-Reviewed Original ResearchAedes aegypti midgutEnteroendocrine cellsSingle-cell RNA sequencingIntestinal stem cellsVirus infectionPathogen interactionsExpressed genesRNA sequencingCopy numberTranscriptomic changesFunctional studiesInfected cellsZika virus infectionEnteroendocrineBlood digestionRNA copy numberCellular levelCell processesGenesMidgutPotential targetCell clustersCellsEnterocytesViral infectionA cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing
Wang S, Huang Y, Wang F, Han Q, Ren N, Wang X, Cui Y, Yuan Z, Xia H. A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing. Scientific Data 2024, 11: 587. PMID: 38839790, PMCID: PMC11153528, DOI: 10.1038/s41597-024-03432-8.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingFat body cellsRNA sequencingSingle-cell levelHemocyte cellsEnteroendocrine cellsVisceral musclesSingle-nucleus resolutionTranscriptome of AeMosquito midgutAedes aegypti midgutMidgut transcriptomeBlood meal digestionCell atlasCardia cellsArbovirus infectionMeal digestionNutrient absorptionMidgut cellsMidgutBody cellsCell clustersPrimary vectorSequenceCellsInvestigating gene functions and single-cell expression profiles of de novo variants in orofacial clefts
Itai T, Yan F, Liu A, Dai Y, Iwaya C, Curtis S, Leslie E, Simon L, Jia P, Chen X, Iwata J, Zhao Z. Investigating gene functions and single-cell expression profiles of de novo variants in orofacial clefts. Human Genetics And Genomics Advances 2024, 5: 100313. PMID: 38807368, PMCID: PMC11318074, DOI: 10.1016/j.xhgg.2024.100313.Peer-Reviewed Original ResearchDe novo variantsCPO geneOMIM genesGene functionScRNA-seq data analysisOrofacial cleftsMan (OMIMScRNA-seq analysisOnline Mendelian InheritanceSingle-cell RNA sequencingSingle-cell expression profilesInvestigate gene functionCleft palateScRNA-seqGene setsCellular expression profilesMendelian inheritanceGenetic variantsRNA sequencingOrofacial clefting genesContextual geneGenesExpression patternsCongenital birth defectsExpression profilesIntegrating phylogenies into single-cell RNA sequencing analysis allows comparisons across species, genes, and cells
Church S, Mah J, Dunn C. Integrating phylogenies into single-cell RNA sequencing analysis allows comparisons across species, genes, and cells. PLOS Biology 2024, 22: e3002633. PMID: 38787797, PMCID: PMC11125556, DOI: 10.1371/journal.pbio.3002633.Peer-Reviewed Original ResearchConceptsScRNA-seqPhylogenetic comparative approachCellular gene expressionScRNA-seq analysisSingle-cell RNA sequencingRNA sequencing analysisGene treesSpecies treeCell phylogenyPhylogenetic approachPhylogenetic treeEvolutionary historyPairwise alignmentSingle-cell RNA sequencing analysisSequence analysisCellular lifeRNA sequencingGene expressionGenesCell evolutionCell lineagesPhylogenySpeciesCell functionCellsImmunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection
Cinco I, Napier E, Rhoades N, Davies M, Allison D, Kohama S, Bermudez L, Winthrop K, Fuss C, Spindel E, Messaoudi I. Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection. MBio 2024, 15: e00829-24. PMID: 38771046, PMCID: PMC11237422, DOI: 10.1128/mbio.00829-24.Peer-Reviewed Original ResearchConceptsNTM pulmonary diseaseIncreased disease severityNontuberculous mycobacteriaDisease severityBacterial DNAAged animalsAntigen-specific T cellsPulmonary diseaseAssociated with increased disease severityDysregulated macrophage responsePersistence of bacterial DNALack of animal modelsRhesus macaquesSingle-cell RNA sequencingNontuberculous mycobacterial infectionsImmune cell infiltrationRhesus macaque modelBacterial loadAged rhesus macaquesTesting novel therapeuticsRight caudal lobeLower respiratory microbiomeYears of ageMAH infectionMicrobial communitiesSingle-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer
Wang L, Izadmehr S, Sfakianos J, Tran M, Beaumont K, Brody R, Cordon-Cardo C, Horowitz A, Sebra R, Oh W, Bhardwaj N, Galsky M, Zhu J. Single-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer. IScience 2024, 27: 109928. PMID: 38812546, PMCID: PMC11133924, DOI: 10.1016/j.isci.2024.109928.Peer-Reviewed Original ResearchScRNA-seqTumor microenvironmentUrothelial cancerRNA sequencingRNA-seq datasetsRNA-seq dataSingle-cellSingle-cell RNA sequencingMinor cell typesCohorts treated with immune checkpoint inhibitorsResistance to immune checkpoint blockadeImmune checkpoint blockade resistanceCheckpoint blockade resistanceImmune checkpoint blockadeImmune checkpoint inhibitorsTumor microenvironment heterogeneityFeatures associated with poor outcomeSpatial genomicsHuman urothelial cancerInfluence tumor progressionClinically relevant insightsCheckpoint blockadeCheckpoint inhibitorsTreatment responseCell typesNKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing
Xie G, Toledo M, Hu X, Yong H, Sanchez P, Liu C, Naji A, Irianto J, Wang Y. NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing. BMC Genomics 2024, 25: 427. PMID: 38689254, PMCID: PMC11059690, DOI: 10.1186/s12864-024-10335-w.Peer-Reviewed Original ResearchConceptsSingle-nucleus RNA sequencingRNA sequencingNuclei sortingSnRNA-seqGene expressionEndocrine populationsFluorescence-activated nuclei sortingHuman isletsGene expression librariesNuclei isolation protocolSingle-cell RNA sequencingFrozen archival tissuesIsolated human isletsHuman pancreatic endocrine cellsSingle-cell transcriptomicsTranscriptomic studiesCytoplasmic contaminationTranscriptome profilingConclusionsOur workNKX2-2Isolated nucleiRNA integrityLiving cellsIsolation protocolPancreatic endocrine cells
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