Featured Publications
m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liver
2024
Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAkt
2022
Spatial profiling of chromatin accessibility in mouse and human tissues
Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 2022, 609: 375-383. PMID: 35978191, PMCID: PMC9452302, DOI: 10.1038/s41586-022-05094-1.Peer-Reviewed Original ResearchConceptsChromatin accessibilityATAC-seqSpecific epigenetic landscapesChromatin accessibility profilingCell fate decisionsEpigenetic informationEpigenetic landscapeGenome scaleFate decisionsAccessible genomeCell identityEpigenetic underpinningsNext-generation sequencingGene regulatorsCell statesMouse embryosSpatial biologySpatial transcriptomicsCell typesCellular levelImmune cell typesDistinct organizationHuman tissuesProfilingSpatial profiling
2019
Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice
Xavier-Ferrucio J, Scanlon V, Li X, Zhang PX, Lozovatsky L, Ayala-Lopez N, Tebaldi T, Halene S, Cao C, Fleming MD, Finberg KE, Krause DS. Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice. Blood 2019, 134: 1547-1557. PMID: 31439541, PMCID: PMC6839952, DOI: 10.1182/blood.2019002039.Peer-Reviewed Original ResearchConceptsMK lineage commitmentExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwayMegakaryocytic-erythroid progenitorsBone marrow transplantation assaysSignal transduction analysisIron-deficient conditionsGene expression analysisMegakaryocytic commitmentLineage commitmentTransferrin receptor 2MK lineageTmprss6-/- miceIron sensorExpression analysisKinase pathwayTransduction analysisTransplantation assaysErythroid progenitorsMarrow environmentHematopoietic cellsMessenger RNAPhospho-ERK1/2Systemic iron deficiencyLow iron
2016
Cooperative Activity of GABP with PU.1 or C/EBPε Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation
Malu K, Garhwal R, Pelletier MG, Gotur D, Halene S, Zwerger M, Yang ZF, Rosmarin AG, Gaines P. Cooperative Activity of GABP with PU.1 or C/EBPε Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation. The Journal Of Immunology 2016, 197: 910-922. PMID: 27342846, PMCID: PMC5022553, DOI: 10.4049/jimmunol.1402285.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCAAT-Enhancer-Binding ProteinsCell DifferentiationCell NucleusChromatin ImmunoprecipitationElectrophoretic Mobility Shift AssayGA-Binding Protein Transcription FactorGene Expression RegulationGranulocytesHEK293 CellsHematopoietic Stem CellsHumansImmunoblottingMiceMice, Inbred C57BLMutagenesis, Site-DirectedProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionReceptors, Cytoplasmic and NuclearSignal TransductionTrans-ActivatorsConceptsLamin B receptorTranscription factorsGene expressionInner nuclear membrane proteinNuclear membrane proteinsFamily transcription factorsNuclear envelope proteinsETS transcription factorsExpression of genesRole of ETSTranscriptional regulatorsTranscriptional activationCombinatorial actionMembrane proteinsLBR geneEts siteEarly myeloid progenitorsCCAAT enhancerGABPSuch cooperative interactionsNeutrophil differentiationGenesMyeloid progenitorsReceptor gene expressionPromoter
2010
Serum response factor is an essential transcription factor in megakaryocytic maturation
Halene S, Gao Y, Hahn K, Massaro S, Italiano JE, Schulz V, Lin S, Kupfer GM, Krause DS. Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood 2010, 116: 1942-1950. PMID: 20525922, PMCID: PMC3173990, DOI: 10.1182/blood-2010-01-261743.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCell DifferentiationCell LineageCells, CulturedCytoskeletonFemaleFlow CytometryGene Expression ProfilingLuminescent ProteinsMaleMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, Electron, TransmissionPlatelet CountPlatelet Factor 4Reverse Transcriptase Polymerase Chain ReactionSerum Response FactorThrombocytopeniaTranscription FactorsConceptsSerum response factorCytoskeletal genesTranscription factorsMADS-box transcription factorsRole of SRFNormal megakaryocyte maturationAbnormal actin distributionResponse factorEssential transcription factorNormal Mendelian frequencyMegakaryocyte developmentMuscle differentiationPF4-Cre miceStress fibersMegakaryocyte maturationMegakaryocytic maturationActin distributionMegakaryocytic lineageMendelian frequencyMegakaryocyte progenitorsVivo assaysCFU-MKGenesPlatelet productionCritical role
2009
C/EBPε directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx
Halene S, Gaines P, Sun H, Zibello T, Lin S, Khanna-Gupta A, Williams SC, Perkins A, Krause D, Berliner N. C/EBPε directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx. Experimental Hematology 2009, 38: 90-103.e4. PMID: 19925846, PMCID: PMC2827304, DOI: 10.1016/j.exphem.2009.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCCAAT-Enhancer-Binding ProteinsCell DifferentiationCell LineChemotaxis, LeukocyteGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorGranulocytesHematopoietic Stem CellsHomeodomain ProteinsMiceMice, KnockoutMonocytesMyelopoiesisNeutrophilsReceptors, ChemokineTranscription FactorsTransduction, GeneticConceptsKO cellsNew regulatory functionCommon myeloid progenitorsNeutrophil-specific granule deficiencyProgenitor cell lineCell linesRestoration of expressionDifferentiated cell linesSpecific granule deficiencyLineage-specific cell surface antigensLineage decisionsLineage determinationEpsilon geneCCAAT enhancerDeficiency phenotypeRegulatory functionsChemotaxis defectIntermediate cell typeKO bone marrowPerformed expressionNeutrophil differentiationCell typesFunctional studiesNeutrophil maturationMyeloid progenitors