2023
Assay optimization for the objective quantification of human multilineage colony-forming units
Thompson E, Carlino M, Scanlon V, Grimes H, Krause D. Assay optimization for the objective quantification of human multilineage colony-forming units. Experimental Hematology 2023, 124: 36-44.e3. PMID: 37271449, PMCID: PMC10527702, DOI: 10.1016/j.exphem.2023.05.007.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingLineage potentialCommon myeloid progenitorsHigh-throughput microscopyMultilineage colony-forming unitsProportion of coloniesSpecific growth factorsCFU assayColony-forming unit assaysMultipotent progenitorsProgenitor populationsLineage outputSitu immunofluorescenceMegakaryocytic lineageMK cellsMegakaryocytic cellsCell typesMyeloid progenitorsProgenitor cellsCell morphologyCell sortingUnit assaysIL-3Colony typesCulture conditions
2020
Differentiation of PTH-Expressing Cells From Human Pluripotent Stem Cells
Lawton BR, Martineau C, Sosa JA, Roman S, Gibson CE, Levine MA, Krause DS. Differentiation of PTH-Expressing Cells From Human Pluripotent Stem Cells. Endocrinology 2020, 161: bqaa141. PMID: 32810225, PMCID: PMC7505176, DOI: 10.1210/endocr/bqaa141.Peer-Reviewed Original Research
2019
Epithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability
Scanlon VM, Teixeira AM, Tyagi T, Zou S, Zhang PX, Booth CJ, Kowalska MA, Bao J, Hwa J, Hayes V, Marks MS, Poncz M, Krause DS. Epithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability. Thrombosis And Haemostasis 2019, 119: 744-757. PMID: 30861547, PMCID: PMC6599679, DOI: 10.1055/s-0039-1679908.Peer-Reviewed Original ResearchConceptsConditional knockout miceKnockout micePlatelet aggregationE-cadherinClot stabilityClot stabilizationSynthase kinase 3β activationAntibody-mediated platelet depletionVivo injury modelsNull plateletsPlatelet productionWild-type miceTail bleeding timeAkt/GSK3βMurine platelet aggregationKnockout mouse modelPlatelet dysfunctionFibrin depositionInjury modelPlatelet depletionPrimary human plateletsBleeding timeMouse modelPlatelet numberE-cadherin antibody
2017
Hematopoietic defects in response to reduced Arhgap21
Xavier-Ferrucio J, Ricon L, Vieira K, Longhini AL, Lazarini M, Bigarella CL, Franchi G, Krause DS, Saad STO. Hematopoietic defects in response to reduced Arhgap21. Stem Cell Research 2017, 26: 17-27. PMID: 29212046, PMCID: PMC6084430, DOI: 10.1016/j.scr.2017.11.014.Peer-Reviewed Original ResearchConceptsErythroid commitmentProgenitor cellsSerial bone marrow transplantationHuman primary cellsProtein familyRho GTPasesHematopoietic progenitor cellsPhenotypic HSCsRho GTPaseHematopoietic defectsRhoC activityNegative regulatorARHGAP21Hematopoietic stemHematopoietic cellsMyeloid progenitorsProgenitor coloniesPrimary cellsBone marrow cellsCancer cellsFunctional aspectsHaploinsufficient miceMarrow cellsCellsGTPases
2016
The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfection
2015
Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis
Sui Z, Nowak RB, Sanada C, Halene S, Krause DS, Fowler VM. Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis. Blood 2015, 126: 520-530. PMID: 25964668, PMCID: PMC4513252, DOI: 10.1182/blood-2014-09-601484.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsApoptosisBlood PlateletsBlotting, WesternCell MembraneCell ProliferationCells, CulturedCytoplasmEmbryo, MammalianFemaleFluorescent Antibody TechniqueHematopoiesisHemorrhageImmunoprecipitationMegakaryocytesMiceMice, KnockoutMicroscopy, ConfocalMicroscopy, Electron, TransmissionMicroscopy, FluorescencePloidiesPolymerizationTropomodulinConceptsPlatelet biogenesisDemarcation membrane systemF-actinTropomodulin-3Organelle distributionProplatelet formationActin polymerizationF-actin cappingF-actin organizationF-actin cytoskeletonWild-type megakaryocytesActin cytoskeletonActin organizationMK differentiationTmod isoformsLarge proplateletsBiogenesisContractile bundlesActin filamentsDMS formationBinds tropomyosinBud sizeMK numberConfocal microscopyCytoskeleton
2013
Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator
Zhang PX, Murray TS, Villella VR, Ferrari E, Esposito S, D'Souza A, Raia V, Maiuri L, Krause DS, Egan ME, Bruscia EM. Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator. The Journal Of Immunology 2013, 190: 5196-5206. PMID: 23606537, PMCID: PMC3711148, DOI: 10.4049/jimmunol.1201607.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCaveolin 1Cells, CulturedChildChild, PreschoolCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFemaleHeme Oxygenase-1HumansInflammationLipopolysaccharidesLung DiseasesMacrophagesMaleMembrane ProteinsMiceMice, KnockoutNasal PolypsReactive Oxygen SpeciesSignal TransductionToll-Like Receptor 4Young AdultConceptsCav-1 expressionHeme oxygenase-1Dysfunctional cystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulatorCell surfaceFibrosis transmembrane conductance regulatorProtein caveolin-1Cellular redox statusCell surface localizationCellular oxidative stateTransmembrane conductance regulatorHO-1 enzymePositive feed-forward loopCystic fibrosis macrophagesNegative regulatorCaveolin-1Conductance regulatorCell survivalHO-1 deliverySurface localizationRedox statusMΦ responsesHO-1/CO pathwayPathwayPotential targetDynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging
Megyola CM, Gao Y, Teixeira AM, Cheng J, Heydari K, Cheng E, Nottoli T, Krause DS, Lu J, Guo S. Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging. Stem Cells 2013, 31: 895-905. PMID: 23335078, PMCID: PMC4309553, DOI: 10.1002/stem.1323.Peer-Reviewed Original ResearchConceptsCell-cell interactionsEarly reprogrammingDynamic cell-cell interactionsSingle-cell resolutionTime-lapse microscopyE-cadherin inhibitionTime-lapse imagingPluripotency inductionInduced pluripotencyGranulocyte-monocyte progenitorsPluripotent cellsReprogrammingMolecular mechanismsCell resolutionCell migrationCellular interactionsGenetic makeupE-cadherinSatellite coloniesExperimental systemHematopoietic stateSource cellsRare cellsColoniesComplex mechanisms
2012
MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation
Smith EC, Thon JN, Devine MT, Lin S, Schulz VP, Guo Y, Massaro SA, Halene S, Gallagher P, Italiano JE, Krause DS. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood 2012, 120: 2317-2329. PMID: 22806889, PMCID: PMC3447785, DOI: 10.1182/blood-2012-04-420828.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCells, CulturedCrosses, GeneticCytoplasmCytoskeletonGene Expression ProfilingHematopoiesisMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisPlatelet ActivationThrombocytopeniaTrans-ActivatorsTranscription FactorsConceptsMegakaryocyte maturationPlatelet formationSerum response factorSerum response factor expressionMembrane organizationGene expressionMKL1MKL2Response factorDKO miceKO backgroundMegakaryocyte compartmentMegakaryocytesCritical roleMegakaryocyte ploidyExpressionMaturationKnockout miceFactor expressionCrucial roleHomologuesGenesMiceProlonged bleeding timeRoleRole of RhoA-Specific Guanine Exchange Factors in Regulation of Endomitosis in Megakaryocytes
Gao Y, Smith E, Ker E, Campbell P, Cheng EC, Zou S, Lin S, Wang L, Halene S, Krause DS. Role of RhoA-Specific Guanine Exchange Factors in Regulation of Endomitosis in Megakaryocytes. Developmental Cell 2012, 22: 573-584. PMID: 22387001, PMCID: PMC3306542, DOI: 10.1016/j.devcel.2011.12.019.Peer-Reviewed Original ResearchConceptsGEF-H1Efficient platelet productionExchange factor GEF-H1Guanine exchange factorGEF-H1 knockdownDevelopment of aneuploidyGEF-H1 expressionMK polyploidizationExchange factorPloidy defectsAberrant mitosisDevelopmental processesExogenous expressionPolyploidizationRhoA activationEndomitotic cyclePrimary cellsUnknown mechanismMechanistic insightsECT2EndomitosisAneuploid cancersPlatelet productionMegakaryocytesDownregulationProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets
Truman LA, Bentley KL, Smith EC, Massaro SA, Gonzalez DG, Haberman AM, Hill M, Jones D, Min W, Krause DS, Ruddle NH. ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets. American Journal Of Pathology 2012, 180: 1715-1725. PMID: 22310467, PMCID: PMC3349900, DOI: 10.1016/j.ajpath.2011.12.026.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal MedullaAnimalsBlood PlateletsCells, CulturedCytoplasmEndothelial CellsGene Expression RegulationGenotypeGlycoproteinsHomeodomain ProteinsLuminescent ProteinsLymph NodesLymphatic VesselsMegakaryocytesMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMicroscopy, FluorescenceTumor Cells, CulturedTumor Suppressor ProteinsConceptsLymph nodesLymphatic vesselsAdrenal medullaExpression of Prox1Tumor metastasisHigh endothelial venulesProx1 expressionTwo-photon laser scanning microscopyTransplant rejectionDentate gyrusEndothelial venulesAntigen presentationC57BL/6 backgroundTransgenic miceLipid metabolismMiceNeuroendocrine cellsAdult liverNovel siteMetastasisMedullaStudy of diseasesLiving mouseUnknown rolePotential utility
2011
Activation of autophagy in mesenchymal stem cells provides tumor stromal support
Sanchez CG, Penfornis P, Oskowitz AZ, Boonjindasup AG, Cai DZ, Dhule SS, Rowan BG, Kelekar A, Krause DS, Pochampally RR. Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis 2011, 32: 964-972. PMID: 21317300, PMCID: PMC3128555, DOI: 10.1093/carcin/bgr029.Peer-Reviewed Original ResearchConceptsSD-MSCsStromal cellsMesenchymal stem cellsMultipotential mesenchymal stem cellsMCF-7 tumor growthBreast cancer cell proliferationStem cellsVivo tumor xenograftsMCF-7 breast cancer cellsCancer cell proliferationSolid tumor survivalBreast cancer cellsBeclin-1 stainingActivation of autophagyAnti-apoptotic factorsTime-dependent increaseUpregulation of autophagySolid tumor microenvironmentBreast cancerImmunodeficient miceTumor xenograftsSolid tumorsTumor growthParacrine factorsSurvival mechanism
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
Adenosine inhibits chemotaxis and induces hepatocyte‐specific genes in bone marrow mesenchymal stem cells
Mohamadnejad M, Sohail MA, Watanabe A, Krause DS, Swenson ES, Mehal WZ. Adenosine inhibits chemotaxis and induces hepatocyte‐specific genes in bone marrow mesenchymal stem cells. Hepatology 2009, 51: 963-973. PMID: 20044808, PMCID: PMC2840188, DOI: 10.1002/hep.23389.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAnimalsBone Marrow CellsCell DifferentiationCells, CulturedChemotaxisHepatocytesMesenchymal Stem CellsMiceConceptsMarrow-derived mesenchymal stem cellsHepatocyte growth factorMSC chemotaxisCellular injuryMesenchymal stem cellsAdenosine concentrationRegulation of HGFInhibition of HGFEffects of adenosineSite of injuryBone marrow-derived mesenchymal stem cellsHepatocyte-specific genesHigh adenosine concentrationsHuman marrow-derived mesenchymal stem cellsAdenosine monophosphateBone marrow mesenchymal stem cellsStem cellsMarrow mesenchymal stem cellsConcentration of adenosineLiver injuryCytosolic calcium signalingStress fiber formationA2A receptorsHepatocyte-like cellsCyclic adenosine monophosphateDynamics of α-globin locus chromatin structure and gene expression during erythroid differentiation of human CD34+ cells in culture
Mahajan MC, Karmakar S, Newburger PE, Krause DS, Weissman SM. Dynamics of α-globin locus chromatin structure and gene expression during erythroid differentiation of human CD34+ cells in culture. Experimental Hematology 2009, 37: 1143-1156.e3. PMID: 19607874, PMCID: PMC2997688, DOI: 10.1016/j.exphem.2009.07.001.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-GlobinsAntigens, CD34CCCTC-Binding FactorCells, CulturedChromatin Assembly and DisassemblyEnhancer Elements, GeneticErythroid Precursor CellsErythropoiesisErythropoietinGATA1 Transcription FactorGene Expression Regulation, DevelopmentalGlycophorinsHematopoietic Cell Growth FactorsHistonesHumansInsulator ElementsNF-E2 Transcription Factor, p45 SubunitProtein BindingRepressor ProteinsRNA Polymerase IITranscription FactorsConceptsAlpha-globin lociTranscription factor recruitmentChromatin structureGATA-1Transcription factorsErythroid differentiationGene expressionFactor recruitmentPol IIQuantitative polymerase chain reaction analysisAlpha-globin gene expressionKey erythroid transcription factorsErythroid transcription factorsNF-E2Chromatin immunoprecipitation-quantitative polymerase chain reaction analysisAlpha-globin genesUpstream activator sitesBeta-like genesPolymerase chain reaction analysisChain reaction analysisStages of erythropoiesisGlobin promoterDifferent differentiation stagesFactor CTCFHistone modificationsRole for MKL1 in megakaryocytic maturation
Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, Tuck D, Schulz V, Mane SM, Berliner N, Sun Y, Morris SW, Qiu C, Krause DS. Role for MKL1 in megakaryocytic maturation. Blood 2009, 113: 2826-2834. PMID: 19136660, PMCID: PMC2661865, DOI: 10.1182/blood-2008-09-180596.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Cell CountBone MarrowCell DifferentiationCell Line, TumorCells, CulturedDNA-Binding ProteinsGene Expression ProfilingGene Expression RegulationHumansLeukemia, Erythroblastic, AcuteMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOncogene Proteins, FusionPloidiesRecombinant Fusion ProteinsRNA InterferenceRNA, Small InterferingSerum Response FactorThrombocytopeniaThrombopoiesisThrombopoietinTrans-ActivatorsConceptsMegakaryoblastic leukemia 1Reduced platelet countsSerum response factorMegakaryocytic differentiationPeripheral bloodPlatelet countMKL1 expressionMegakaryoblastic leukemiaBone marrow megakaryocytesMuscle cellsPresence of thrombopoietinPhysiologic maturationHuman erythroleukemia cell lineIncreased numberMarrow megakaryocytesCell linesErythroleukemia cell lineMegakaryocytesMegakaryocytic maturationDifferentiated muscle cellsOverexpressionConcurrent increaseMuscle differentiationCellsMaturation
2008
Influence of Culture Medium on Smooth Muscle Cell Differentiation from Human Bone Marrow–Derived Mesenchymal Stem Cells
Gong Z, Calkins G, Cheng EC, Krause D, Niklason LE. Influence of Culture Medium on Smooth Muscle Cell Differentiation from Human Bone Marrow–Derived Mesenchymal Stem Cells. Tissue Engineering Part A 2008, 15: 319-330. PMID: 19115826, PMCID: PMC2716410, DOI: 10.1089/ten.tea.2008.0161.Peer-Reviewed Original ResearchMacrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice
Bruscia EM, Zhang PX, Ferreira E, Caputo C, Emerson JW, Tuck D, Krause DS, Egan ME. Macrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice. American Journal Of Respiratory Cell And Molecular Biology 2008, 40: 295-304. PMID: 18776130, PMCID: PMC2645527, DOI: 10.1165/rcmb.2008-0170oc.Peer-Reviewed Original ResearchConceptsExaggerated inflammatory responseExaggerated immune responseBone marrow-derived macrophagesIL-6Marrow-derived macrophagesCystic fibrosisCF miceKeratinocyte chemoattractantCytokine responsesInflammatory responseIL-1alphaImmune responseAlveolar macrophagesBronchoalveolar lavage fluidGranulocyte colony-stimulating factorNumber of neutrophilsChemoattractant protein-1CF lung diseaseElevated cytokine responseInnate immune systemImportant therapeutic targetCF mouse modelsPopulation of macrophagesColony-stimulating factorPseudomonas aeruginosa LPS
1997
Regulation of CD34 expression in differentiating M1 cells.
Krause DS, Kapadia SU, Raj NB, May WS. Regulation of CD34 expression in differentiating M1 cells. Experimental Hematology 1997, 25: 1051-61. PMID: 9293902.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsAntigens, CD34Base SequenceBinding SitesCell DifferentiationCells, CulturedDNA-Binding ProteinsDown-RegulationGene Expression RegulationGene Expression Regulation, DevelopmentalGene Expression Regulation, NeoplasticHematopoiesisLeukemia, MyeloidMiceMolecular Sequence DataNuclear ProteinsRNA, MessengerTranscription, GeneticConceptsTranscription initiation siteUntranslated regionPromoter activityHematopoietic stemCell type-specific expressionSecondary structureTATA-less promoterPromoter-luciferase reporter constructsFull promoter activityUpstream genomic DNAProgenitor cellsTranslation start siteMature blood cellsType-specific expressionOptimal promoter activityExtensive secondary structureP1 nuclease digestionCell-specific factorsTranscriptional initiationGene regulationTranscription factorsConsensus sitesStart siteRegulatory elementsTATA element