2024
Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue.
Venkat A, Carlino M, Lawton B, Prasad M, Amodio M, Gibson C, Zeiss C, Youlten S, Krishnaswamy S, Krause D. Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue. Genome Research 2024, 34: 837-850. PMID: 38977309, PMCID: PMC11293540, DOI: 10.1101/gr.278215.123.Peer-Reviewed Original ResearchCell statesMitochondrial transcript abundanceParathyroid glandsHuman parathyroidCell-cell communication analysisRNA expression analysisSingle-cell analysisTranscriptional dynamicsTranscript abundanceExpression dynamicsRNA transcriptomeEpithelial cell statesCell abundanceExpression analysisPseudotime analysisAn immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors
Zhang X, Song B, Carlino M, Li G, Ferchen K, Chen M, Thompson E, Kain B, Schnell D, Thakkar K, Kouril M, Jin K, Hay S, Sen S, Bernardicius D, Ma S, Bennett S, Croteau J, Salvatori O, Lye M, Gillen A, Jordan C, Singh H, Krause D, Salomonis N, Grimes H. An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors. Nature Immunology 2024, 25: 703-715. PMID: 38514887, PMCID: PMC11003869, DOI: 10.1038/s41590-024-01782-4.Peer-Reviewed Original ResearchSurface markersLeukemia stem cell populationHematopoietic progenitor compartmentBone marrow cellsHuman bone marrow cellsHuman hematopoietic progenitorsCell surface markersStem cell populationCITE-seqClinical responseHematopoietic progenitorsMarrow cellsProgenitor compartmentCellular Indexing of TranscriptomesTransitional cellsCell populationsProgenitor analysisCellular indicesMultimodal approachGenomics programsProgenitor stateTranscriptome profilingSurface proteinsProgenitorsCell states
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 conditions3092 – 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 therapyTherapyRecruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetMultiparameter 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 assaysStructure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization.
Reed FE, Eskow NM, Min E, Carlino M, Mancuso R, Kwon N, Smith EC, Larsuel ST, Wang L, Scanlon V, Krause DS. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022 PMID: 36005559.Peer-Reviewed Original ResearchStructure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization
Reed F, Eskow N, Min E, Carlino M, Mancuso R, Kwon N, Smith E, Larsuel S, Wang L, Scanlon V, Krause D. Structure-function analysis of the role of megakaryoblastic leukemia 1 in megakaryocyte polyploidization. Haematologica 2022, 107: 2972-2976. PMID: 36453520, PMCID: PMC9713552, DOI: 10.3324/haematol.2021.280499.Peer-Reviewed Original ResearchGene therapy applications to transfusion medicine
Tabibi S, Gehrie E, Bruscia E, Krause D. Gene therapy applications to transfusion medicine. 2022, 642-647. DOI: 10.1002/9781119719809.ch56.ChaptersGene therapyVector-based gene therapyViral vector-based gene therapyGene therapy applicationsTranscription activator-like effector nucleasesZinc finger nucleasesGene-editing approachesNonviral vectorsGene-editing techniquesGene integrationTherapy applicationsFinger nucleasesEffector nucleasesViral vectorsReplication-competent virusPossible applicationsGenetic materialApplicationsNucleaseTarget cellsVectorCRISPRRecruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis
Di Pietro C, Öz HH, Zhang PX, Cheng EC, Martis V, Bonfield TL, Kelley TJ, Jubin R, Abuchowski A, Krause DS, Egan ME, Murray TS, Bruscia EM. Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis. Experimental & Molecular Medicine 2022, 54: 639-652. PMID: 35581352, PMCID: PMC9166813, DOI: 10.1038/s12276-022-00770-8.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Cystic fibrosisOxygenase-1Myeloid differentiation factor 88Neutrophilic pulmonary inflammationChronic airway infectionDifferentiation factor 88HO-1 levelsDisease mouse modelPseudomonas aeruginosaRecruitment of monocytesResolution of inflammationMonocytes/macrophagesTreatment of CFConditional knockout miceMechanism of actionLung neutrophiliaNeutrophilic inflammationLung inflammationAirway infectionPulmonary diseasePulmonary inflammationFactor 88Lung damageProinflammatory cytokines
2021
558: Carbon monoxide–based therapy primes macrophages to express HO-1 and to resolve lung hyper-inflammation in cystic fibrosis
Pietro C, Öz H, Zhang P, Cheng E, Martis V, Bonfield T, Kelley T, Jubin R, Abuchowski A, Krause D, Egan M, Murray T, Bruscia E. 558: Carbon monoxide–based therapy primes macrophages to express HO-1 and to resolve lung hyper-inflammation in cystic fibrosis. Journal Of Cystic Fibrosis 2021, 20: s263-s264. DOI: 10.1016/s1569-1993(21)01981-0.Peer-Reviewed Original ResearchMethylation 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 inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivationBone Marrow-Derived VSELs Engraft as Lung Epithelial Progenitor Cells after Bleomycin-Induced Lung Injury
Ciechanowicz AK, Sielatycka K, Cymer M, Skoda M, Suszyńska M, Bujko K, Ratajczak MZ, Krause DS, Kucia M. Bone Marrow-Derived VSELs Engraft as Lung Epithelial Progenitor Cells after Bleomycin-Induced Lung Injury. Cells 2021, 10: 1570. PMID: 34206516, PMCID: PMC8303224, DOI: 10.3390/cells10071570.Peer-Reviewed Original ResearchConceptsBronchioalveolar stem cellsOrganoid assaysAT2 cellsStem cellsH2B-GFP fusion proteinLung epithelial progenitor cellsProgenitor cellsEmbryonic-like stem cellsSurfactant protein CSmall embryonic-like stem cellsEpithelial progenitor cellsLung injuryNonhematopoietic stem cellsFusion proteinAlveolar type 2 cellsPhysiological potentialProgenitor activityBleomycin-Induced Lung InjuryH2B-GFP miceWT recipient miceRegenerative functionSPC promoterType 2 cellsVSELsReporter miceCombined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMiceSingle 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 readoutMRTFA: A critical protein in normal and malignant hematopoiesis and beyond
Reed F, Larsuel ST, Mayday MY, Scanlon V, Krause DS. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. Journal Of Biological Chemistry 2021, 296: 100543. PMID: 33722605, PMCID: PMC8079280, DOI: 10.1016/j.jbc.2021.100543.Peer-Reviewed Original ResearchConceptsMalignant hematopoiesisActin cytoskeleton dynamicsCritical cellular functionsResponse factorSerum response factorTranscription factor ACellular rolesImmediate early genesProtein partnersTranscriptional regulationCytoskeleton dynamicsCellular functionsTranscriptional targetsTranscription factorsCytoskeletal proteinsCritical proteinsMRTFAEarly genesCell typesChromosomal translocationsHematopoietic cellsCell growthFactor AHematopoiesisMuscle cells
2020
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, Krause DS, Lee AI, Halene S, Martin KA, Chun HJ, Hwa J. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nature Reviews Cardiology 2020, 18: 194-209. PMID: 33214651, PMCID: PMC7675396, DOI: 10.1038/s41569-020-00469-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdministration, InhalationAnticoagulantsBlood Coagulation DisordersBlood Platelet DisordersCOVID-19COVID-19 Drug TreatmentEndothelium, VascularEndothelium-Dependent Relaxing FactorsEpoprostenolHeart Disease Risk FactorsHumansIloprostInflammationNitric OxidePlatelet Aggregation InhibitorsSARS-CoV-2Systemic Inflammatory Response SyndromeThrombosisThrombotic MicroangiopathiesVascular DiseasesVasodilator AgentsVenous ThromboembolismConceptsCardiovascular risk factorsRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2Pre-existing cardiovascular diseaseAcute respiratory syndrome coronavirus 2Traditional cardiovascular risk factorsAcute respiratory distress syndromeRespiratory syndrome coronavirus 2Respiratory distress syndromeManagement of patientsSyndrome coronavirus 2COVID-19 pathologyCoronavirus disease 2019Potential therapeutic strategyCytokine stormEndothelial dysfunctionThrombotic complicationsDistress syndromeExcessive inflammationCoronavirus 2Severe outcomesAdvanced ageCardiovascular diseaseDisease 2019Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants.
Kwon N, Thompson EN, Mayday MY, Scanlon V, Lu YC, Krause DS. Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants. Current Opinion In Hematology 2020, 28: 28-35. PMID: 33186151, PMCID: PMC7737300, DOI: 10.1097/moh.0000000000000625.Peer-Reviewed Original ResearchConceptsMegakaryocyte-erythroid progenitorsFate decisionsCell fate decisionsMegakaryocytic-erythroid progenitorsGene expression patternsProgenitor cell biologyFate determinantsFate determinationCurrent understandingTranscription factorsCell biologyExpression patternsPluripotent progenitorsProgenitorsModel systemExtrinsic factorsBiologyDisease statesFateDevelopment leadEpigeneticsMegakaryocytesUnderstandingDiscoveryIsolation