2024
SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING
De Man R, Adams T, McDonough J, Cala-Garcia J, Moss B, Yan X, Rosas I, Kaminski N. SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING. Innovation In Aging 2024, 8: 571-572. PMCID: PMC11690935, DOI: 10.1093/geroni/igae098.1872.Peer-Reviewed Original ResearchSomatic mutationsMutational burdenCell type annotationAlveolar type 1DNA damage response genesAnalysis of somatic mutationsSomatic mutation accumulationAccumulation of somatic mutationsCell typesUbiquitin ligase geneDamage response genesLoss of cell functionAnalyzed somatic mutationsDecreased expressionSingle-cell RNAseqLigase geneMutation accumulationTop genesSignaling genesCell marker genesResponse genesTranscriptional changesAlveolar type 1 cellsGenesMarker genes
2022
Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvantMutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in CholangiocarcinomaMutant-IDH1 Promotes Immunoevasion in Cholangiocarcinoma
Wu M, Shi L, Dubrot J, Merritt J, Vijay V, Wei T, Kessler E, Olander K, Adil R, Pankaj A, Tummala K, Weeresekara V, Zhen Y, Wu Q, Luo M, Shen W, García-Beccaria M, Fernández-Vaquero M, Hudson C, Ronseaux S, Sun Y, Saad-Berreta R, Jenkins R, Wang T, Heikenwälder M, Ferrone C, Goyal L, Nicolay B, Deshpande V, Kohli R, Zheng H, Manguso R, Bardeesy N. Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in CholangiocarcinomaMutant-IDH1 Promotes Immunoevasion in Cholangiocarcinoma. Cancer Discovery 2022, 12: 812-835. PMID: 34848557, PMCID: PMC8904298, DOI: 10.1158/2159-8290.cd-21-1077.Peer-Reviewed Original ResearchConceptsTumor maintenanceKetoglutarate-dependent enzymesDiscovery of mechanismsDNA demethylaseResponse genesCell-specific ablationCTLA4 blockadeMouse modelEnzyme inhibitsImmune checkpoint activationCytotoxic T-cell functionTumor cellsSuppression of CD8T-cell depletionIssue featureT cell activityT cell recruitmentT cell functionNew therapeutic strategiesInterferon γ expressionIsocitrate dehydrogenase 1 (IDH1) mutationTET2Receptor 1Γ expressionInhibitor efficacy
2021
Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions
Chandrasekaran S, Espeso-Gil S, Loh YE, Javidfar B, Kassim B, Zhu Y, Zhang Y, Dong Y, Bicks LK, Li H, Rajarajan P, Peter CJ, Sun D, Agullo-Pascual E, Iskhakova M, Estill M, Lesch BJ, Shen L, Jiang Y, Akbarian S. Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions. Nature Communications 2021, 12: 7243. PMID: 34903713, PMCID: PMC8669064, DOI: 10.1038/s41467-021-26862-z.Peer-Reviewed Original ResearchConceptsCellular stress response genesOpen chromatin domainsChromatin domain organizationRepeat-rich sequencesStress response genesRetrotransposon expansionsSPRET/EiJChromatin domainsChromosomal architectureChromosomal conformationDomain organizationAdult mouse cerebral cortexMurine germlineTranscriptional dysregulationResponse genesRegulatory mechanismsMus musculusMature neuronsNeuronal ablationStrong enrichmentMouse cerebral cortexSequenceSETDB1Single moleculesGermlineThe butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation
Jeong J, Kadegowda AKG, Meyer TJ, Jenkins LM, Dinan JC, Wysolmerski JJ, Weigert R, Mather IH. The butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation. FASEB BioAdvances 2021, 3: 971-997. PMID: 34938960, PMCID: PMC8664049, DOI: 10.1096/fba.2021-00059.Peer-Reviewed Original ResearchWild-type cellsAcute phase response genesCell death pathwaysMouse linesFos/JunMutant mouse linesMammary epitheliumMammary epithelial cellsButyrophilin 1A1Secretion complexDeath routeProteomic analysisNuclear DNADeath pathwaysResponse genesOptimal milk productionExpression of cyclinsCaspase-8Upregulation of Ki67Cell deathMembrane receptorsType cellsLipid dropletsRedox enzymesLysosomal lysisImpaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function
Thompson B, Chen Y, Davidson EA, Garcia-Milian R, Golla JP, Apostolopoulos N, Orlicky DJ, Schey K, Thompson DC, Vasiliou V. Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function. The Ocular Surface 2021, 22: 190-203. PMID: 34425299, PMCID: PMC8560581, DOI: 10.1016/j.jtos.2021.08.010.Peer-Reviewed Original ResearchConceptsHEK293T cellsEye developmentGSH biosynthesisTransactivation activityPax6 functionReactive oxygen speciesSubsequent gene ontologyCell identity genesButhionine sulfoximineEpithelial cell identityRNA-seq analysisIngenuity Pathway AnalysisKey upstream regulatorIdentity genesCell identityGene OntologyRNA-seqImmune response genesBioinformatics analysisResponse genesGlutathione biosynthesisLens morphogenesisMolecular consequencesUpstream regulatorMicrophthalmia phenotypeC. elegans discriminates colors to guide foraging
Ghosh DD, Lee D, Jin X, Horvitz HR, Nitabach MN. C. elegans discriminates colors to guide foraging. Science 2021, 371: 1059-1063. PMID: 33674494, PMCID: PMC8554940, DOI: 10.1126/science.abd3010.Peer-Reviewed Original ResearchConceptsCellular stress response genesCellular stress response pathwaysStress response genesStress response pathwaysPhotoreceptor genesDiverse phylaC. elegansForaging decisionsResponse pathwaysResponse genesForagingOpsinGenesPhotosensitive cellsNatural environmentCaenorhabditisHarmful bacteriaElegansPhylaOrganismsBacteriaPathwayRoundwormsCellsToxinEthanol production process driving changes on industrial strains
Nagamatsu ST, Coutouné N, José J, Fiamenghi MB, Pereira GAG, de Castro Oliveira J, Carazzolle MF. Ethanol production process driving changes on industrial strains. FEMS Yeast Research 2021, 21: foaa071. PMID: 33417685, DOI: 10.1093/femsyr/foaa071.Peer-Reviewed Original ResearchConceptsMain evolutionary driversEthanol production processMore robust strainsStress response genesSugarcane fermentationEthanol titerEthanol RedEthanol productionEvolutionary driversIndustrial yeastIndustrial fermentationMaltose transporterGenome adaptationEngineering strategiesPhylogenetic treeCorn fermentationPositive selectionSaccharomyces cerevisiaeMetal homeostasisIndustrial strainsResponse genesBiofuel productionRobust strainsNumber of copiesGenes
2020
Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells
Marczyk M, Patwardhan GA, Zhao J, Qu R, Li X, Wali VB, Gupta AK, Pillai MM, Kluger Y, Yan Q, Hatzis C, Pusztai L, Gunasekharan V. Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells. Cancers 2020, 12: 2551. PMID: 32911681, PMCID: PMC7563413, DOI: 10.3390/cancers12092551.Peer-Reviewed Original ResearchTriple-negative breast cancer cellsCancer cellsBreast cancer cellsStress response genesMulti-omics landscapeCell population compositionDrug-induced cell deathMulti-omics investigationsCell linesBCL2 family inhibitorsSingle-cell analysisChromatin accessibilityGenome structureMDA-MB-231 triple-negative breast cancer cellsChromatin structureMethylation stateResponse genesFamily inhibitorsCell deathTNBC cell linesNumber variationsDefense mechanismsResistance mechanismsNew therapeutic strategiesGenesAnalysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain
Schmidt-Kastner R, Guloksuz S, Kietzmann T, van Os J, Rutten B. Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain. Frontiers In Psychiatry 2020, 11: 393. PMID: 32477182, PMCID: PMC7235330, DOI: 10.3389/fpsyt.2020.00393.Peer-Reviewed Original ResearchObstetric complicationsIschemia-hypoxiaHypoxia-inducible factorNervous systemSynaptic functionMonogenic disordersFocal brain ischemiaGenome-wide association studiesChi-square testSCZ genesEarly brain developmentBrain ischemiaMental disordersMutation-intolerant genesBrain developmentSCZ genome-wide association studySynaptic genesDisordersBh geneSchizophreniaBrainGene setsResponse genesSchizophrenia genesSubset
2018
Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts
Farshchian M, Matin M, Armant O, Geerts D, Dastpak M, Nakhaei-Rad S, Tajeran M, Jebelli A, Shahriyari M, Bahrami M, Fallah A, Yaghoobi V, Mirahmadi M, Abbaszadegan M, Bahrami A. Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts. Cytokine 2018, 106: 1-11. PMID: 29501710, DOI: 10.1016/j.cyto.2018.02.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCellular ReprogrammingChromosomal Proteins, Non-HistoneDNA Transposable ElementsDown-RegulationEmbryo, MammalianEndogenous RetrovirusesFibroblastsGene Regulatory NetworksHEK293 CellsHumansImmunity, InnateMice, Inbred BALB CModels, BiologicalOctamer Transcription Factor-3Promoter Regions, GeneticRepressor ProteinsRNA, Double-StrandedRNA, Long NoncodingRNA-Binding ProteinsConceptsEmbryonic stem cellsResponse genesGerm cell-specific genesDeep transcriptome analysisGerm cell developmentCell-specific genesStem cellsMouse embryonic fibroblastsTransposon suppressionDsRNA-2Interferon response genesTranscriptome analysisSelf-renewal capacityEndogenous retrotransposonsEmbryonic fibroblastsCell developmentNanos2Antiviral genesGenesInnate immune systemGene cassettesInnate immunityImmune responseCritical pathwaysFirst report
2017
Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria
Matsuyama M, Martins A, Shallom S, Kamenyeva O, Kashyap A, Sampaio E, Kabat J, Olivier K, Zelazny A, Tsang J, Holland S. Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 241-252. PMID: 28915071, PMCID: PMC5806000, DOI: 10.1165/rcmb.2017-0218oc.Peer-Reviewed Original ResearchConceptsCholesterol biosynthesisUpregulation of genesRespiratory epitheliumGene expression signaturesCiliary genesTranscriptional responseRNA sequencingEpithelial cell infectionResponse genesInflammatory response genesHost responseCytokine/chemokine productionRespiratory epithelial cell culturesEpithelial cell culturesPulmonary nontuberculous mycobacteria (NTM) diseaseExpression signaturesMajor host responsesCytokines/chemokinesGenesRespiratory epithelial cellsCiliary functionNontuberculous mycobacteria diseaseCell infectionMultiplicity of infectionBiosynthesis
2016
Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity
Babayev E, Wang T, Szigeti-Buck K, Lowther K, Taylor HS, Horvath T, Seli E. Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity. Maturitas 2016, 93: 121-130. PMID: 27523387, PMCID: PMC5064871, DOI: 10.1016/j.maturitas.2016.06.015.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesUnfolded protein response genesProtein response genesMitochondrial DNAMitochondrial dynamicsMitochondrial stressResponse genesMammalian reproductionMitochondria morphologyStressful conditionsMitochondrial changesMitochondriaROS levelsMtDNA levelsElevated expressionMtDNA quantityOxygen speciesOocytesGenesMature oocytesNumerous aspectsExpressionReproductive agingMII oocytesFollicle-enclosed oocytesTranscription factor ICBP90 regulates the MIF promoter and immune susceptibility locus
Yao J, Leng L, Sauler M, Fu W, Zheng J, Zhang Y, Du X, Yu X, Lee P, Bucala R. Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus. Journal Of Clinical Investigation 2016, 126: 732-744. PMID: 26752645, PMCID: PMC4731159, DOI: 10.1172/jci81937.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCCAAT-Enhancer-Binding ProteinsGenetic LociGenetic Predisposition to DiseaseHumansIntramolecular OxidoreductasesJurkat CellsMacrophage Migration-Inhibitory FactorsMicrosatellite RepeatsPolymorphism, GeneticPromoter Regions, GeneticTranscription, GeneticUbiquitin-Protein LigasesConceptsTranscription factorsMacrophage migration inhibitory factorWhole-genome transcription analysisOligonucleotide affinity chromatographyLength-dependent mannerTranscriptional regulationFunctional insightsTranscription analysisNuclear proteinsImmune response genesPolymorphic lociMIF promoterResponse genesNuclear lysatesKey regulatorHigher mRNA levelsMajor proteinsSusceptibility lociTranscriptionCytokine macrophage migration inhibitory factorLociExpression levelsCommon allelesMigration inhibitory factorMicrosatellite polymorphism
2014
Global gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue
Aktas B, Sun H, Yao H, Shi W, Hubbard R, Zhang Y, Jiang T, Ononye SN, Wali VB, Pusztai L, Symmans WF, Hatzis C. Global gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue. Molecular Oncology 2014, 8: 717-727. PMID: 24602449, PMCID: PMC4048748, DOI: 10.1016/j.molonc.2014.02.002.Peer-Reviewed Original ResearchConceptsGlobal gene expression changesGlobal gene expressionGene expression changesGenomic signaturesResponse genesGene expressionSensitive transcriptsExpression changesStress response genesCell cycle regulationSignificant transcriptional changesExpression levelsCycle regulationTranscriptional changesIndividual probe setsInduced transcriptsAffected transcriptsProtein processingEnrichment analysis
2012
Sex-specific gene expression during asexual development of Neurospora crassa
Wang Z, Kin K, López-Giráldez F, Johannesson H, Townsend JP. Sex-specific gene expression during asexual development of Neurospora crassa. Fungal Genetics And Biology 2012, 49: 533-543. PMID: 22626843, PMCID: PMC3397379, DOI: 10.1016/j.fgb.2012.05.004.Peer-Reviewed Original ResearchConceptsMating-type genesAsexual developmentMating typesNeurospora crassaGene expressionSex-specific gene expressionFungal life historyLight-responsive genesOverall gene expressionExpression levelsDifferent mating typesExpression of pheromonePheromone genesHigh expression levelsMat AType genesLife historyResponse genesExpression differencesDevelopment stagesGenesClonal developmentImpact of lightReceptor geneCrassa
2010
The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch
Hellman NE, Liu Y, Merkel E, Austin C, Le Corre S, Beier DR, Sun Z, Sharma N, Yoder BK, Drummond IA. The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18499-18504. PMID: 20937855, PMCID: PMC2972951, DOI: 10.1073/pnas.1005998107.Peer-Reviewed Original ResearchConceptsCilia functionTektin-1Primary response geneRole of ciliaKidney cyst formationEpithelial stretchRenal cyst formationCiliogenic genesTranscriptional networksFoxj1a expressionDevelopmental patterningTranscriptional regulatorsTissue damageKidney ischemia-reperfusion injuryTranscription factorsFoxj1aOrgan homeostasisResponse genesCilia genesUncharacterized componentsCyst formationPronephric tubulesAcute kidney injuryIschemia-reperfusion injuryCilia motility
2009
Control of Inducible Gene Expression by Signal-Dependent Transcriptional Elongation
Hargreaves D, Horng T, Medzhitov R. Control of Inducible Gene Expression by Signal-Dependent Transcriptional Elongation. Journal Of End-to-End-testing 2009, 138: 129-145. DOI: 10.1016/s9999-9994(09)20368-0.Peer-Reviewed Original ResearchTranscriptional elongationP-TEFbSignal-dependent recruitmentProtein-coding transcriptsRNA polymerase IIInducible transcriptional programSecondary response genesInducible gene expressionNew protein synthesisMultiple cell typesCorepressor complexChromatin remodelingHistone modificationsPolymerase IIPol IIMRNA processingTranscriptional programsProtein BRD4Unspliced transcriptsKinetics of expressionResponse genesUnique regulationGene expressionEssential functionsProtein synthesis
2006
The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica
Tu X, Latifi T, Bougdour A, Gottesman S, Groisman EA. The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 13503-13508. PMID: 16938894, PMCID: PMC1557385, DOI: 10.1073/pnas.0606026103.Peer-Reviewed Original ResearchConceptsSigma factor RpoSPhoP/PhoQTwo-component systemAlternative sigma factor RpoSTwo-component regulatory system PhoP/PhoQPhoP/PhoQ.Stress response genesSalmonella enterica serovar TyphimuriumRpoS stabilityClpXP proteaseTranscriptional activatorEnterica serovar TyphimuriumRegulatory circuitsRpoS mutantResponse genesRegulatory proteinsProtein turnoverRpoSBacterial speciesEscherichia coliPhoP geneGenesSerovar TyphimuriumE. coliPhoQ
2001
Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock.
Gallouzi IE, Brennan CM, Steitz JA. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA 2001, 7: 1348-61. PMID: 11565755, PMCID: PMC1370177, DOI: 10.1017/s1355838201016089.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAntigens, SurfaceCarrier ProteinsCytoplasmELAV ProteinsELAV-Like Protein 1Fatty Acids, UnsaturatedHeat-Shock ResponseHeLa CellsHumansKaryopherinsLigandsNeuropeptidesNuclear ProteinsPhosphoproteinsReceptors, Cytoplasmic and NuclearRNA-Binding ProteinsRNA, MessengerConceptsAU-rich elementsNuclear exportHeat shockMessenger RNANuclear export factor CRM1Protein ligandsInhibitor of CRM1Export factor CRM1CRM1-dependent exportMRNA nuclear exportRNA-binding proteinProtein-protein interactionsRapid mRNA turnoverEarly response genesAssociation of HuRHeat shock inducesCytoplasmic fociHnRNP complexesExport pathwayMRNA turnoverLeptomycin BCoimmunoprecipitation experimentsCytoplasmic interactionsNES domainResponse genes
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