2021
Methylation of dual-specificity phosphatase 4 controls cell differentiation
Su H, Jiang M, Senevirathne C, Aluri S, Zhang T, Guo H, Xavier-Ferrucio J, Jin S, Tran NT, Liu SM, Sun CW, Zhu Y, Zhao Q, Chen Y, Cable L, Shen Y, Liu J, Qu CK, Han X, Klug CA, Bhatia R, Chen Y, Nimer SD, Zheng YG, Iancu-Rubin C, Jin J, Deng H, Krause DS, Xiang J, Verma A, Luo M, Zhao X. Methylation of dual-specificity phosphatase 4 controls cell differentiation. Cell Reports 2021, 36: 109421. PMID: 34320342, PMCID: PMC9110119, DOI: 10.1016/j.celrep.2021.109421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArginineCell DifferentiationCell LineChildDual-Specificity PhosphatasesEnzyme StabilityFemaleHEK293 CellsHumansMaleMAP Kinase Signaling SystemMegakaryocytesMethylationMice, Inbred C57BLMiddle AgedMitogen-Activated Protein Kinase PhosphatasesMyelodysplastic SyndromesP38 Mitogen-Activated Protein KinasesPolyubiquitinProtein-Arginine N-MethyltransferasesProteolysisRepressor ProteinsUbiquitinationYoung AdultConceptsDual-specificity phosphataseCell differentiationSingle-cell transcriptional analysisP38 MAPKControls cell differentiationE3 ligase HUWE1Knockdown screeningMK differentiationTranscriptional analysisMegakaryocyte differentiationProtein kinaseP38 axisP38 activationPRMT1Transcriptional signatureContext of thrombocytopeniaMK cellsMechanistic insightsPharmacological inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivationSingle cell epigenetic visualization assay
Kint S, Van Criekinge W, Vandekerckhove L, De Vos WH, Bomsztyk K, Krause DS, Denisenko O. Single cell epigenetic visualization assay. Nucleic Acids Research 2021, 49: e43-e43. PMID: 33511400, PMCID: PMC8096246, DOI: 10.1093/nar/gkab009.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineAcetylationCell LineDNA MethylationEarly Growth Response Protein 1Epigenesis, GeneticEpigenomicsFemaleGene Expression RegulationGene SilencingHistonesHIV-1HumansImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceProvirusesReal-Time Polymerase Chain ReactionRNA, Long NoncodingSingle-Cell AnalysisConceptsEpigenetic marksEpigenetic statusGene allelesFemale somatic cellsCurrent sequencing approachesGene of interestGene-specific oligonucleotidesQuantitative fluorescent readoutTranscription stateRNA FISHHuman cell linesSomatic cellsTranscription statusTarget genesSequencing approachH3K9ac levelsDifferent genesGenesIndividual cellsAntibody-conjugated alkaline phosphataseDNA oligosSingle cellsCell linesSame cellsFluorescent readout
2019
Promoters to Study Vascular Smooth Muscle
Chakraborty R, Saddouk FZ, Carrao AC, Krause DS, Greif DM, Martin KA. Promoters to Study Vascular Smooth Muscle. Arteriosclerosis Thrombosis And Vascular Biology 2019, 39: 603-612. PMID: 30727757, PMCID: PMC6527360, DOI: 10.1161/atvbaha.119.312449.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell LineCell LineageCell TransdifferentiationGene Expression RegulationGene Knockout TechniquesGene TargetingHumansMiceMicrofilament ProteinsMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleMyofibroblastsMyosin Heavy ChainsNeovascularization, PathologicNeovascularization, PhysiologicPhenotypePromoter Regions, GeneticRecombinant Fusion ProteinsConceptsSmooth muscle cellsCre driver linesDiversity of phenotypesMuscle cell typesVisceral smooth muscle cellsSMC transdifferentiationActa2 promoterRemarkable plasticityExciting new eraSMC functionCell typesCre linesEmbryonic heartExciting discoveriesPhenotypeMuscle cellsPerivascular adipocytesPromoterVascular smooth muscleNonmuscular cellsExpressionMyeloid cellsCardiovascular phenotypesCellsBlood vessel wall
2017
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages
Di Pietro C, Zhang PX, O’Rourke T, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM. Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletal ProteinsDisease Models, AnimalMacrophage ActivationMacrophagesMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionToll-Like Receptor 4ConceptsCystic fibrosis transmembrane conductance regulatorPI3K/AktFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorPI3K/Akt signalingConductance regulatorAnti-bacterial immune responseAkt signalingAltered localizationEzrinCystic fibrosis diseaseMφ activationAktProtein levelsFibrosis diseaseActivationImmune regulationPhagocytosisInductionDirect linkSignalingRegulatorImmune responseMΦMacrophages
2016
In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, López-Giráldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM. In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery. Nature Communications 2016, 7: 13304. PMID: 27782131, PMCID: PMC5095181, DOI: 10.1038/ncomms13304.Peer-Reviewed Original ResearchConceptsNanoparticle deliveryGene correctionReversal of splenomegalyPeptide nucleic acidLow off-target effectsVivo correctionGenome editingOff-target effectsGene editingHaematopoietic stem cellsNucleic acidsDonor DNAStem cellsΓPNAΒ-thalassaemiaNanoparticlesDeliveryEditingSCF treatmentTriplex formation
2013
Effect of a Matrigel Sandwich on Endodermal Differentiation of Human Embryonic Stem Cells
Lawton BR, Sosa JA, Roman S, Krause DS. Effect of a Matrigel Sandwich on Endodermal Differentiation of Human Embryonic Stem Cells. Stem Cell Reviews And Reports 2013, 9: 578-585. PMID: 23719997, DOI: 10.1007/s12015-013-9447-2.Peer-Reviewed Original ResearchMeSH KeywordsCell Culture TechniquesCell DifferentiationCell LineCell LineageCell MovementCell SurvivalCollagenDrug CombinationsEmbryonic Stem CellsEndodermFluorescent Antibody TechniqueGene Expression Regulation, DevelopmentalGlutamine-Fructose-6-Phosphate Transaminase (Isomerizing)Hepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 3-betaHumansLamininProteoglycansReceptors, Cell SurfaceReverse Transcriptase Polymerase Chain ReactionSOXF Transcription FactorsTime FactorsConceptsHuman embryonic stem cellsEmbryonic stem cellsDefinitive endodermEndodermal differentiationGene expression patternsStem cellsPrecardiac mesodermExpression patternsLow-serum mediumCell deathMesenchymal transitionMigratory characteristicsKey eventsEndodermDifferentiationCell viabilityActivin ASerum mediumCellsGastrulationImproved protocolMesodermInductionGenesNutrients
2012
Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms
Guo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16636-16641. PMID: 23012470, PMCID: PMC3478612, DOI: 10.1073/pnas.1213196109.Peer-Reviewed Original ResearchAnimalsBone Marrow CellsBone Marrow NeoplasmsBone Marrow TransplantationCell LineColony-Forming Units AssayDoxycyclineFlow CytometryGene Expression Regulation, NeoplasticGranulocyte-Macrophage Colony-Stimulating FactorInterleukin-3Leukocytes, MononuclearMiceMice, Inbred C57BLMicroRNAsMyeloproliferative DisordersOncogenesReverse Transcriptase Polymerase Chain Reaction
2011
Targeted Gene Modification of Hematopoietic Progenitor Cells in Mice Following Systemic Administration of a PNA-peptide Conjugate
Rogers FA, Lin SS, Hegan DC, Krause DS, Glazer PM. Targeted Gene Modification of Hematopoietic Progenitor Cells in Mice Following Systemic Administration of a PNA-peptide Conjugate. Molecular Therapy 2011, 20: 109-118. PMID: 21829173, PMCID: PMC3255600, DOI: 10.1038/mt.2011.163.Peer-Reviewed Original ResearchConceptsGene modificationGene therapyHematopoietic stem cell gene therapyStem cell gene therapyGenomic modificationsVivo gene therapyCell gene therapyTargeted gene modificationVivo gene modificationHematopoietic progenitor cellsPeptide nucleic acidSystemic administrationBone marrowGene-targeting strategiesProgenitor cellsPrimary recipient miceStem cell mobilizationEx vivo manipulationSickle cell anemiaLymphoid cell lineagesDonor miceRecipient miceHematologic disordersInvasive alternativeCell mobilization
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 progenitorsFanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction
Zhi G, Wilson JB, Chen X, Krause DS, Xiao Y, Jones NJ, Kupfer GM. Fanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction. Cancer Research 2009, 69: 8775-8783. PMID: 19861535, PMCID: PMC5912675, DOI: 10.1158/0008-5472.can-09-2312.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBRCA2 ProteinCell LineCheckpoint Kinase 1DNA DamageFanconi AnemiaFanconi Anemia Complementation Group D2 ProteinFanconi Anemia Complementation Group ProteinsHumansImmunoblottingImmunoprecipitationMass SpectrometryPhosphorylationProtein KinasesSequence Homology, Amino AcidSerineSignal TransductionConceptsS-phase checkpoint kinaseFanconi anemia DNA repair pathwayFanconi anemia pathwayRegulatory phosphorylation eventsDNA repair pathwaysFANCD1/BRCA2Phosphomimetic mutationBRCA2 interactionsPhosphorylation eventsSerine 331Checkpoint kinaseCancer susceptibility syndromeComplementation groupsRepair pathwaysPathway functionFanconi anemiaBone marrow failurePhosphorylationDownstream playersVivo interactionS331Susceptibility syndromeMarrow failurePathwayMonoubiquitylation
2008
Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids
Chin JY, Kuan JY, Lonkar PS, Krause DS, Seidman MM, Peterson KR, Nielsen PE, Kole R, Glazer PM. Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 13514-13519. PMID: 18757759, PMCID: PMC2533221, DOI: 10.1073/pnas.0711793105.Peer-Reviewed Original ResearchConceptsBeta-globin geneEndogenous beta-globin locusSplice site mutationHuman cellsPrimary hematopoietic progenitor cellsBeta-globin locusAltered helical structureHuman beta-globin geneSingle base pair changeSingle base-pair modificationTriplex-forming peptide nucleic acidsDonor DNA moleculesBase pair changesCell cycle stageDisease-related genesDonor DNA fragmentsNucleic acidsProper splicingSite-specific bindingSite-specific modificationMammalian cellsHematopoietic progenitor cellsDNA repairSecond intronGene locus
2002
Development of a murine hematopoietic progenitor complementary DNA microarray using a subtracted complementary DNA library
Ma X, Husain T, Peng H, Lin S, Mironenko O, Maun N, Johnson S, Tuck D, Berliner N, Krause DS, Perkins AS. Development of a murine hematopoietic progenitor complementary DNA microarray using a subtracted complementary DNA library. Blood 2002, 100: 833-844. PMID: 12130493, DOI: 10.1182/blood.v100.3.833.Peer-Reviewed Original ResearchConceptsMyeloid cell differentiationCell differentiationCDNA libraryGene expressionPrimary murine bone marrow cellsSignal transduction genesTypes of genesMurine bone marrow cellsComplementary DNA cloneGenomewide expression analysisStem cell differentiationComplementary DNA libraryComplementary DNA microarrayEML cellsTransduction genesHematopoietic genesUncharacterized ESTsSequence tagsDistinct genesDNA libraryDNA clonesTranscription factorsBone marrow-derived progenitorsExpression analysisDNA microarrays
1998
Normal neutrophil differentiation and secondary granule gene expression in the EML and MPRO cell lines.
Lawson ND, Krause DS, Berliner N. Normal neutrophil differentiation and secondary granule gene expression in the EML and MPRO cell lines. Experimental Hematology 1998, 26: 1178-85. PMID: 9808058.Peer-Reviewed Original ResearchConceptsNeutrophil differentiationDominant-negative retinoic acid receptor alphaCell linesNormal neutrophil differentiationRetinoic acid receptor alphaCD11b/CD18Macrophage colony-stimulating factorDownregulation of CD34Granulocyte/macrophage colony-stimulating factorTrans retinoic acidAcid receptor alphaColony-stimulating factorNeutrophil gelatinaseGranulocytic differentiation programReceptor alphaSerum-free mediumAppropriate cytokinesMyeloid lineageRetinoic acidInduces expressionLeukemic myelopoiesisHL60MyelopoiesisNeutrophilic differentiationDifferentiation program
1997
Multilineage gene expression precedes commitment in the hemopoietic system.
Hu M, Krause D, Greaves M, Sharkis S, Dexter M, Heyworth C, Enver T. Multilineage gene expression precedes commitment in the hemopoietic system. Genes & Development 1997, 11: 774-785. PMID: 9087431, DOI: 10.1101/gad.11.6.774.Peer-Reviewed Original ResearchConceptsGene expression programsMultilineage gene expressionLineage specificationExpression programsGene activityLocus activationMultipotential stateGene expressionCytokine receptorsHemopoietic stemGranulocytic lineageProgenitor cellsSingle-cell RT-PCRSame cellsHemopoietic systemRT-PCRExclusive commitmentCell RT-PCRCellsLineagesCoexpressionDifferentiationExpressionStemActivation