2022
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2019
Gene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE)
Meng H, Yaari G, Bolen CR, Avey S, Kleinstein SH. Gene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE). PLOS Computational Biology 2019, 15: e1006899. PMID: 30939133, PMCID: PMC6461294, DOI: 10.1371/journal.pcbi.1006899.Peer-Reviewed Original Research
2015
Analysis of gene–environment interactions in postnatal development of the mammalian intestine
Rakoff-Nahoum S, Kong Y, Kleinstein SH, Subramanian S, Ahern PP, Gordon JI, Medzhitov R. Analysis of gene–environment interactions in postnatal development of the mammalian intestine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1929-1936. PMID: 25691701, PMCID: PMC4343130, DOI: 10.1073/pnas.1424886112.Peer-Reviewed Original ResearchConceptsTLR/IL-1RToll-like receptorsPostnatal developmentIntestinal gene expressionMyeloid differentiation factor 88Domain-containing adapter-inducing interferonDifferentiation factor 88Adapter-inducing interferonMast cell homeostasisIntestinal ontogenyReceptor family membersFactor 88WT miceGene expression programsSmooth muscle developmentGene-environment interactionsIL-1RIntestinal physiologyImmune systemKnockout littermatesPostnatal transitionMicrobial colonizationIntestinal contentsGene expressionPubertal maturation
2014
DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell Lymphoma
Xi Y, Shivarov V, Yaari G, Kleinstein S, Strout M. DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell Lymphoma. Blood 2014, 124: 3549. DOI: 10.1182/blood.v124.21.3549.3549.Peer-Reviewed Original ResearchActivation-induced cytidine deaminaseDNA demethylationGene expressionDNA methylationMethylation sitesBisulfite sequencingBL2 cellsHumanHT-12 v4 Expression BeadChipPrimary transcriptional start sitesC-terminal deletion mutantsCpG sitesGenome-wide methylation profilingActive DNA demethylationMethylation statusRNA polymerase IISomatic cell differentiationCytidine deaminaseSingle-nucleotide resolutionTranscriptional start siteSubset of genesDNA repair pathwaysList of genesTarget gene expressionEarly cell developmentV4 Expression BeadChipDynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression
Bolen CR, Ding S, Robek MD, Kleinstein SH. Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology 2014, 59: 1262-1272. PMID: 23929627, PMCID: PMC3938553, DOI: 10.1002/hep.26657.Peer-Reviewed Original ResearchConceptsGene expressionExpression profilingIndividual interferonMicroarray-based gene expression profilingDynamic expression profilingGene expression profilingSimilar signaling cascadesPotential specific rolesPromoter analysisTranscriptional responseHuh7 hepatoma cellsGene inductionExpression hierarchySignaling cascadesIFN-α signalingAntiviral stateNegative feedback mechanismType IPrimary human hepatocytesHepatoma cellsISG inductionSpecific roleGenesInterferon-stimulated gene inductionSuperior clinical activity
2011
Gene Expression Gradients along the Tonotopic Axis of the Chicken Auditory Epithelium
Frucht CS, Uduman M, Kleinstein SH, Santos-Sacchi J, Navaratnam DS. Gene Expression Gradients along the Tonotopic Axis of the Chicken Auditory Epithelium. Journal Of The Association For Research In Otolaryngology 2011, 12: 423-435. PMID: 21399991, PMCID: PMC3123449, DOI: 10.1007/s10162-011-0259-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCalcium ChannelsChickensCyclic AMP-Dependent Protein KinasesGene Expression ProfilingGene Expression Regulation, DevelopmentalHair Cells, AuditoryLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsMicroRNAsModels, AnimalOrgan of CortiProtein Kinase CSodium ChannelsConceptsGene expression gradientsAuditory epitheliumKinases protein kinase CChicken auditory epitheliumExpression gradientsAvian auditory epitheliumBasilar papillaFold-change cutoffActivity of kinasesIon channel genesProtein kinase CChicken basilar papillaGene setsGenetic basisEnrichment analysisExpression patternsGene expressionGeneSpring softwareChannel genesMechanism of inductionKinase CGenesMicroarray dataDifferential activityQuantitative PCR
2010
Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation
Frucht CS, Uduman M, Duke JL, Kleinstein SH, Santos-Sacchi J, Navaratnam DS. Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation. PLOS ONE 2010, 5: e11502. PMID: 20634979, PMCID: PMC2901389, DOI: 10.1371/journal.pone.0011502.Peer-Reviewed Original ResearchConceptsNew hair cellsAuditory epitheliumChicken auditory epitheliumHair cellsInner ear developmentHair cell regenerationGene expression analysisAuditory hair cellsEar developmentExpression analysisMyosin VIEnrichment analysisCycle controlGene expressionMolecular eventsSingle microRNAMediator of proliferationRelevant pathwaysFunctional experimentsPost-hatch chicksRegenerating tissueMammalsGenesBrdU incorporationCell regeneration
2008
Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*
Pagliaccetti NE, Eduardo R, Kleinstein SH, Mu XJ, Bandi P, Robek MD. Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*. Journal Of Biological Chemistry 2008, 283: 30079-30089. PMID: 18757365, PMCID: PMC2662072, DOI: 10.1074/jbc.m804296200.Peer-Reviewed Original ResearchConceptsAntiviral gene expressionIFN-alpha/betaIL-29IFN-alphaVirus replicationIFN-gammaInhibits Hepatitis C Virus ReplicationCritical innate immune responseAntiviral activityHepatitis C virus replicationChronic viral infectionsC virus replicationGreater antiviral activityInnate immune responseIFN-gamma combinationHepatitis CGene expressionCellular antiviral responseCytokines interleukinHCV replicationImmune responseViral infectionIndividual cytokinesVesicular stomatitis virusAntiviral response