2023
3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS
Mancuso R, Thompson E, Wang L, Krause D. 3092 – CRISPR OPTIMIZATION TO SCREEN FOR GENES THAT REGULATE FATE SPECIFICATION OF PRIMARY HUMAN HEMATOPOIETIC PROGENITORS. Experimental Hematology 2023, 124: s96. DOI: 10.1016/j.exphem.2023.06.199.Peer-Reviewed Original ResearchFate specificationMCherry fluorescent reporterFluorescent reportersNumber of genesLarge-scale screenDNA-PK inhibitorPrimary human hematopoietic progenitorsHuman hematopoietic progenitorsCD45-negative cellsPanel of genesCRISPR screensErythroid maturationSingle guideMolecular mechanismsGRNAGRNA sequencesNegative cellsGenesHematopoietic progenitorsLentiviral transductionTotal RNAReporterProgenitorsTransfectionCell number3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION
Kwon N, Lu Y, Thompson E, Wang L, Zhang P, Krause D. 3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION. Experimental Hematology 2023, 124: s104. DOI: 10.1016/j.exphem.2023.06.215.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsFate specificationHEL cellsGene expressionSingle-cell RNA-seq dataPost-translational modificationsDifferential gene expressionRNA-seq dataChromatin localizationRNA-seqPhosphorylation statusRUNX1 overexpressionE progenitorsTranscriptional activityKey regulatorRUNX1 mRNAMK progenitorsT residuesGenesErythroid progenitorsRUNX1MKPProgenitorsProtein levelsSpecification mechanism
2022
Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure
Qu R, Kluger Y, Yang J, Zhao J, Hafler D, Krause D, Bersenev A, Bosenberg M, Hurwitz M, Lucca L, Kluger H. Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure. Molecular Cancer 2022, 21: 219. PMID: 36514045, PMCID: PMC9749221, DOI: 10.1186/s12943-022-01688-5.Peer-Reviewed Original ResearchConceptsAdoptive cell therapySingle-cell analysisDepth single-cell analysisSingle-cell RNAACT productsDisease progressionT-cell receptor sequencingCell therapyFamily genesFeatures of exhaustionMultiple tumor typesCell expansionGenesNew clonotypesTIL preparationsClonal cell expansionCytokine therapyTreatment failureSerial bloodClonesEffector functionsSerial samplesTumor typesCellular therapyTherapy
2021
Single 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
MKL1-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
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 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
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 timeRole
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