2022
Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation
Scanlon VM, Thompson EN, Lawton BR, Kochugaeva M, Ta K, Mayday MY, Xavier-Ferrucio J, Kang E, Eskow NM, Lu YC, Kwon N, Laumas A, Cenci M, Lawrence K, Barden K, Larsuel ST, Reed FE, Peña-Carmona G, Ubbelohde A, Lee JP, Boobalan S, Oppong Y, Anderson R, Maynard C, Sahirul K, Lajeune C, Ivathraya V, Addy T, Sanchez P, Holbrook C, Van Ho AT, Duncan JS, Blau HM, Levchenko A, Krause DS. Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation. Scientific Reports 2022, 12: 16218. PMID: 36171423, PMCID: PMC9519589, DOI: 10.1038/s41598-022-19013-x.Peer-Reviewed Original ResearchConceptsMegakaryocytic-erythroid progenitorsFate specificationLineage commitmentUnderstanding of hematopoiesisProgenitor cell biologyPrimary human hematopoietic progenitorsSingle-cell trackingSingle-cell assaysSingle-cell levelHuman hematopoietic progenitorsProgenitor cell dynamicsLineage specificationCell fateColony-forming unit assaysTimelapse imagingSitu fluorescence stainingCell biologyLineage tracingDivision rateCytokine thrombopoietinHematopoietic progenitorsProgenitorsFluorescence stainingCell dynamicsUnit assays
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 inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivation
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
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 ironMKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
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 cellsCellsGTPasesSNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume
Zou S, Teixeira AM, Kostadima M, Astle WJ, Radhakrishnan A, Simon LM, Truman L, Fang JS, Hwa J, Zhang PX, van der Harst P, Bray PF, Ouwehand WH, Frontini M, Krause DS. SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume. PLOS ONE 2017, 12: e0178095. PMID: 28542600, PMCID: PMC5441597, DOI: 10.1371/journal.pone.0178095.Peer-Reviewed Original ResearchConceptsExpression quantitative lociMK maturationGene expressionRho guanine exchange factorsHuman megakaryocytesGenome-wide association studiesDNase I hypersensitive regionGuanine exchange factorHuman genetic studiesExchange factorReporter mouse modelDNase hypersensitivityQuantitative lociPlatelet traitsMK developmentTranscript levelsCausal SNPsHypersensitive regionARHGEF3Human phenotypesAssociation studiesGenetic studiesHematopoietic subpopulationsGenetic variantsSNPs
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
2014
Nonstochastic Reprogramming from a Privileged Somatic Cell State
Guo S, Zi X, Schulz VP, Cheng J, Zhong M, Koochaki SH, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. Nonstochastic Reprogramming from a Privileged Somatic Cell State. Cell 2014, 156: 649-662. PMID: 24486105, PMCID: PMC4318260, DOI: 10.1016/j.cell.2014.01.020.Peer-Reviewed Original ResearchConceptsSomatic cell stateCell statesAcquisition of pluripotencyMurine hematopoietic progenitorsEndogenous Oct4Cell cycle accelerationNonstochastic mannerSomatic cellsProgeny cellsPluripotent fateYamanaka factorsCell cycleHematopoietic progenitorsP53 knockdownPluripotencyReprogrammingCycling populationFactor expressionCellsFibroblastsImportant bottleneckKnockdownProgenitorsFateExpression
2013
Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung
Kassmer SH, Jin H, Zhang PX, Bruscia EM, Heydari K, Lee JH, Kim CF, Kassmer SH, Krause DS. Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung. Stem Cells 2013, 31: 2759-2766. PMID: 23681901, PMCID: PMC4536826, DOI: 10.1002/stem.1413.Peer-Reviewed Original ResearchConceptsEpithelial cellsSmall embryonic-like stem cellsLung epithelial cellsEmbryonic-like stem cellsStem/progenitor cellsStem cellsDonor miceHematopoietic stem/progenitor cellsBM cellsAdult BMBone marrowSmall embryonicNonhematopoietic cellsProgenitor cellsBroad differentiation potentialVSELsEngraftmentLungHigh rateNumerous reportsAdult stem cellsDifferentiation potentialCellsFirst reportReportMolecular Pathways: Induction of Polyploidy as a Novel Differentiation Therapy for Leukemia
Krause DS, Crispino JD. Molecular Pathways: Induction of Polyploidy as a Novel Differentiation Therapy for Leukemia. Clinical Cancer Research 2013, 19: 6084-6088. PMID: 23963861, PMCID: PMC3836832, DOI: 10.1158/1078-0432.ccr-12-2604.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAcute megakaryocytic leukemiaAcute promyelocytic leukemiaDifferentiation therapyForms of AMLSpecific hematologic malignanciesAbnormal hematopoietic cellsTrans retinoic acidPolyploidy inducersTumor burdenMyelodysplastic syndromeHematologic malignanciesEffective therapyInduction of polyploidizationMyeloid leukemiaClinical studiesPromyelocytic leukemiaMegakaryocytic leukemiaPrimary myelofibrosisTherapyLeukemiaDifferentiation of megakaryocytesRetinoic acidMalignancySuch agentsEffect 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 protocolMesodermInductionGenesNutrientsVery small embryonic‐like cells: Biology and function of these potential endogenous pluripotent stem cells in adult tissues
Kassmer SH, Krause DS. Very small embryonic‐like cells: Biology and function of these potential endogenous pluripotent stem cells in adult tissues. Molecular Reproduction And Development 2013, 80: 677-690. PMID: 23440892, PMCID: PMC3740022, DOI: 10.1002/mrd.22168.Peer-Reviewed Original ResearchConceptsEmbryonic-like cellsSmall embryonic-like cellsAdult tissuesCell typesPrimordial germ cellsGerm layer lineagesMarkers of pluripotentSingle-cell levelPluripotent stem cellsCell cycle inhibitory genesSimilar cell typesMurine bone marrowPluripotency genesMurine VSELsNon-hematopoietic cellsCell cycleGerm cellsInhibitory genesStress conditionsStem cellsDifferent phenotypesGenesRegenerative medicineVSELsCells
2012
Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation
Smith EC, Teixeira AM, Chen RC, Wang L, Gao Y, Hahn KL, Krause DS. Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation. Blood 2012, 121: 1094-1101. PMID: 23243284, PMCID: PMC3575755, DOI: 10.1182/blood-2012-05-429993.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell DifferentiationCell Line, TumorCell NucleusDNA-Binding ProteinsEnzyme ActivationHumansMegakaryocyte Progenitor CellsMegakaryocytesMiceOncogene Proteins, FusionProtein MultimerizationRhoA GTP-Binding ProteinSerum Response FactorTetradecanoylphorbol AcetateThrombopoietinTrans-ActivatorsConceptsMegakaryocyte differentiationActin polymerizationSubcellular localizationSerum response factor (SRF) transcriptional activityRhoA activitySRF target genesComplex cellular responsesFactor transcriptional activityMuscle cell typesCell-type specificHuman erythroleukemia cellsPrimary megakaryocytesTranscriptional regulatorsActin organizationCellular functionsTranscriptional functionSRF activityNuclear localizationTarget genesMegakaryocytic differentiationTranscriptional activityNuclear accumulationErythroleukemia cellsMolecular mechanismsRhoA activation
2011
Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors
Qian L, Krause DS, Saltzman WM. Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors. Biotechnology Journal 2011, 7: 440-448. PMID: 21922669, PMCID: PMC3532892, DOI: 10.1002/biot.201100184.Peer-Reviewed Original ResearchTargeted 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
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 roleDetection of bone marrow–derived lung epithelial cells
Kassmer SH, Krause DS. Detection of bone marrow–derived lung epithelial cells. Experimental Hematology 2010, 38: 564-573. PMID: 20447442, PMCID: PMC2909593, DOI: 10.1016/j.exphem.2010.04.011.Peer-Reviewed Original ResearchMeSH KeywordsBone Marrow CellsBone Marrow TransplantationCell DifferentiationCell SeparationEpithelial CellsHumansLungConceptsMarrow-derived epithelial cellsBone marrow-derived cellsMarrow-derived cellsLung epithelial cellsEpithelial cellsBone marrow-derived epithelial cellsDonor bone marrow originBone marrow originBone marrow cellsBlood cell markersNormal tissue repairSpecific cell subsetsCell subsetsGastrointestinal tractTherapeutic benefitMarrow originMultiple organsEpithelial markersDefinitive dataCell markersMarrow cellsProtein expression patternsTissue repairEngraftmentLung
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 progenitorsAdenosine 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 monophosphate