2024
A Short Isoform of Tensin1 Is a Novel Regulator of F-Actin Assembly in Human Erythroblasts That Promotes Enucleation
Fowler V, Ghosh A, Coffin M, Diaz D, Schulz V, Gallagher P. A Short Isoform of Tensin1 Is a Novel Regulator of F-Actin Assembly in Human Erythroblasts That Promotes Enucleation. Blood 2024, 144: 535-535. DOI: 10.1182/blood-2024-210773.Peer-Reviewed Original ResearchRegulation of F-actin assemblyF-actin assemblyF-actinATAC-peaksH3K27 acetylationN-terminal actin-binding domainErythroid differentiationEnucleated cellsActin-binding domainActin-nucleating factorsF-actin cablesActin-binding proteinsTerminal differentiationActin filament polymerizationC-terminal SH2Translation start siteAssemble F-actinFocal adhesion formationDetect F-actinIncreased chromatin accessibilityErythroid terminal differentiationMolecular regulatory mechanismsSpectrin membrane skeletonMRNA translational start siteReduced F-actin
2023
Rps19 and Rpl5 Play Distinct Roles in hematopoietic Stem Cell maintenance and Erythroid Differentiation
Tang Y, Ling T, Khan M, Rao R, Schulz V, Papoin J, Narla A, Lipton J, Palis J, Steiner L, Gallagher P, Narla M, Crispino J, Blanc L. Rps19 and Rpl5 Play Distinct Roles in hematopoietic Stem Cell maintenance and Erythroid Differentiation. Blood 2023, 142: 144. DOI: 10.1182/blood-2023-189146.Peer-Reviewed Original ResearchFailure of erythropoiesisErythroid differentiationVav-iCreHematopoietic stem cell maintenanceFetal hematopoiesisHematopoietic stemProtein translation ratesStem cell maintenanceRibosomal protein haploinsufficiencyGlobal protein synthesisTerminal erythroid differentiationCell compartmentExpression of RUNX1Stem cell compartmentErythroid fateProgenitor cell compartmentFetal liverRibosome biogenesisPolysome profilingNormal expression levelsRibosomal proteinsProgenitor biologyCell maintenanceScRNAseq studiesTranscription factors3189 – REVISITING THE HEMATOPOIETIC AND ERYTHROPOIETIC DEFECTS IN RPS19 AND RPL5 HAPLOINSUFFICIENCY AT THE DEVELOPMENTAL LEVEL
Tang Y, Ling T, Durand S, Palis J, Steiner L, Mohandas N, Gallagher P, Lipton J, Crispino J, Blanc L. 3189 – REVISITING THE HEMATOPOIETIC AND ERYTHROPOIETIC DEFECTS IN RPS19 AND RPL5 HAPLOINSUFFICIENCY AT THE DEVELOPMENTAL LEVEL. Experimental Hematology 2023, 124: s144. DOI: 10.1016/j.exphem.2023.06.296.Peer-Reviewed Original ResearchRibosomal proteinsDiamond-Blackfan anemiaGlobal protein synthesisTerminal erythroid differentiationStem cell exhaustionHematopoietic stem cell exhaustionKey transcription factorInherited bone marrow failure syndromeFailure of erythropoiesisCell cycle arrestHematopoietic developmentMutant cellsTranscription factorsProgenitor stageCRISPR/Erythroid differentiationVav-iCreMendelian ratioDefective erythropoiesisRPS19Bone marrow failure syndromesLoxP sitesProtein synthesisBone marrow failureHematopoietic progenitors
2021
Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency
Wang Y, Li W, Schulz VP, Zhao H, Qu X, Qi Q, Cheng Y, Guo X, Zhang S, Wei X, Liu D, Yazdanbakhsh K, Hillyer CD, Mohandas N, Chen L, Gallagher PG, An X. Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency. Blood 2021, 138: 1615-1627. PMID: 34036344, PMCID: PMC8554652, DOI: 10.1182/blood.2020007401.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationChromatin condensationErythroid differentiationHuman erythroid cellsAcetylation of H4RNA sequencing analysisEnucleation of erythroblastsGroup of enzymesLate-stage erythroblastsErythroid cell culturesHDAC family membersActivation of p53Short hairpin RNAChromatin accessibilityATAC-seqMammalian erythropoiesisH4 deacetylationNonhistone proteinsH4 acetylationDiverse functionsHDAC inhibitor treatmentHuman erythropoiesisKnockdown of HDAC5Erythroid cellsGene expressionComprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis
Yan H, Ali A, Blanc L, Narla A, Lane JM, Gao E, Papoin J, Hale J, Hillyer CD, Taylor N, Gallagher PG, Raza A, Kinet S, Mohandas N. Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis. American Journal Of Hematology 2021, 96: 1064-1076. PMID: 34021930, PMCID: PMC8355124, DOI: 10.1002/ajh.26247.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationHuman erythropoiesisErythroid cellsErythroid progenitorsPrimary bone marrow cellsPrimary erythroid cellsDisorders of erythropoiesisStage-specific defectsErythroid progenitor cellsFunctional insightsProgenitor stageProgenitor populationsHuman bone marrowBone marrowFactor responsivenessNormal erythropoiesisProgenitor cellsBone marrow cellsDiscrete populationsColony assayFlow cytometry-based techniqueDifferentiationProliferative capacityEarly populationAn IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism
Gonzalez-Menendez P, Romano M, Yan H, Deshmukh R, Papoin J, Oburoglu L, Daumur M, Dumé AS, Phadke I, Mongellaz C, Qu X, Bories PN, Fontenay M, An X, Dardalhon V, Sitbon M, Zimmermann VS, Gallagher PG, Tardito S, Blanc L, Mohandas N, Taylor N, Kinet S. An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism. Cell Reports 2021, 34: 108723. PMID: 33535038, PMCID: PMC9169698, DOI: 10.1016/j.celrep.2021.108723.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1Oxidative phosphorylationMitochondrial metabolismReactive oxygen speciesHuman erythroid differentiationHuman erythroid developmentMitochondrial oxidative phosphorylationVitamin C homeostasisHSPC developmentIDH1 knockdownErythroid developmentStepwise differentiationErythroid differentiationLate-stage erythropoiesisTerminal stepCritical regulatorHematopoietic stemMitochondrial superoxideMitochondrial oxidationProgenitor cellsDehydrogenase 1Oxygen speciesCongenital dyserythropoietic anemiaCentral roleDyserythropoietic anemia
2020
Comprehensive proteomic analysis of murine terminal erythroid differentiation
Gautier EF, Leduc M, Ladli M, Schulz VP, Lefèvre C, Boussaid I, Fontenay M, Lacombe C, Verdier F, Guillonneau F, Hillyer CD, Mohandas N, Gallagher PG, Mayeux P. Comprehensive proteomic analysis of murine terminal erythroid differentiation. Blood Advances 2020, 4: 1464-1477. PMID: 32282884, PMCID: PMC7160260, DOI: 10.1182/bloodadvances.2020001652.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationProteomic dataMurine terminal erythroid differentiationTerminal differentiationOverall cellular contentComprehensive proteomic dataComprehensive proteomic analysisMurine erythroid cellsTerminal differentiation processMost biologic processesProteome levelComparison of murineHuman proteomeProteomic analysisTranscriptomic changesChromatin condensationProteomeErythroid cellsFundamental mechanismsRed cell disordersDifferentiation processErythroid progenitorsFriend erythroleukemiaCellular model
2017
Distinct roles for TET family proteins in regulating human erythropoiesis
Yan H, Wang Y, Qu X, Li J, Hale J, Huang Y, An C, Papoin J, Guo X, Chen L, Kang Q, Li W, Schulz VP, Gallagher PG, Hillyer CD, Mohandas N, An X. Distinct roles for TET family proteins in regulating human erythropoiesis. Blood 2017, 129: 2002-2012. PMID: 28167661, PMCID: PMC5383871, DOI: 10.1182/blood-2016-08-736587.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeErythroid differentiationHuman erythropoiesisErythroid progenitorsHuman erythroid differentiationTET family proteinsDistinct rolesKnockdown of TET2Terminal erythroid differentiationHuman erythroid cellsTET2 gene mutationsFamily proteinsTranslocation (TET) familyTET2 knockdownKnockdown experimentsErythroid cellsBiological processesDevelopment defectsTET3TET3 expressionOrthochromatic erythroblastsImpaired differentiationHuman CD34KnockdownTET2
2015
Human and murine erythropoiesis
An X, Schulz VP, Mohandas N, Gallagher PG. Human and murine erythropoiesis. Current Opinion In Hematology 2015, 22: 206-211. PMID: 25719574, PMCID: PMC4401149, DOI: 10.1097/moh.0000000000000134.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationMurine erythropoiesisPerturbed erythropoiesisErythroid differentiationStage-specific programsAlternative splicing programGenome-wide analysisPoor sequence conservationSpecies-specific similaritiesGene expression dataGood model systemSplicing programGenomic methodologiesSequence conservationTranscriptome analysisHuman erythropoiesisExpression dataDifferentiation stageRecent insightsModel systemErythropoiesisDifferentiationFundamental mechanismsCritical insightsDifferent mechanisms
2014
Pomalidomide Modulates Transcription Networks Regulating Human Erythropoiesis and Globin Switching: Implications for Treatment of Hemoglobinopathies
Dulmovits B, Appiah-Kubi A, Papoin J, Gould M, An X, Mohandas N, Gallagher P, Lipton J, Liu J, Blanc L. Pomalidomide Modulates Transcription Networks Regulating Human Erythropoiesis and Globin Switching: Implications for Treatment of Hemoglobinopathies. Blood 2014, 124: 1375. DOI: 10.1182/blood.v124.21.1375.1375.Peer-Reviewed Original ResearchSickle cell diseaseWestern blot analysisΓ-globin productionSide effectsDay 6Painful vaso-occlusive crisesSecond-generation immunomodulatory drugMay-Grunwald Giemsa stainingVaso-occlusive crisisSignificant side effectsQRT-PCRCurrent treatment approachesHbF productionErythroid differentiationBlot analysisFlow cytometric analysisRed cell sicklingMechanism of actionImmunomodulatory drugsNormal samplesPeripheral bloodPharmacologic interventionsCulture systemCell diseaseSimilar doseGlobal transcriptome analyses of human and murine terminal erythroid differentiation
An X, Schulz VP, Li J, Wu K, Liu J, Xue F, Hu J, Mohandas N, Gallagher PG. Global transcriptome analyses of human and murine terminal erythroid differentiation. Blood 2014, 123: 3466-3477. PMID: 24637361, PMCID: PMC4041167, DOI: 10.1182/blood-2014-01-548305.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationErythroid differentiationGene expressionMurine terminal erythroid differentiationStage-specific transcriptomesDifferentiation stageGlobal transcriptome analysisStage-specific patternsRNA sequencing analysisGene expression profilesDistinct developmental stagesMurine transcriptomesFluorescence-activated cell sortingTranscriptional spaceErythroid developmentMurine erythroblastsTranscriptome analysisUnique transcriptomeBioinformatics analysisPerturbed erythropoiesisTranscriptomeExpression profilesErythroid disordersDevelopmental stagesSequencing analysis
2008
Failure of Terminal Erythroid Differentiation in EKLF-Deficient Mice Is Associated with Cell Cycle Perturbation and Reduced Expression of E2F2
Pilon AM, Arcasoy MO, Dressman HK, Vayda SE, Maksimova YD, Sangerman JI, Gallagher PG, Bodine DM. Failure of Terminal Erythroid Differentiation in EKLF-Deficient Mice Is Associated with Cell Cycle Perturbation and Reduced Expression of E2F2. Molecular And Cellular Biology 2008, 28: 7394-7401. PMID: 18852285, PMCID: PMC2593440, DOI: 10.1128/mcb.01087-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell DifferentiationE2F2 Transcription FactorEmbryo, MammalianErythropoiesisGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksKruppel-Like Transcription FactorsLiverMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticStem CellsTranscription, GeneticConceptsErythroid Krüppel-like factorTerminal erythroid differentiationEarly erythroid progenitor cellsErythroid progenitor cellsErythroid differentiationChromatin modifiersProgenitor cellsKrüppel-like transcription factorsNetwork of genesCell cycle regulationChromatin immunoprecipitation analysisKrüppel-like factorCell cycle progressionFailure of erythropoiesisS phase transitionEarly progenitor cellsTranscriptional activatorCycle regulationTranscriptional profilingTranscription factorsTarget genesImmunoprecipitation analysisDNase IErythroid cellsCycle progression
2007
Novel role for EKLF in megakaryocyte lineage commitment
Frontelo P, Manwani D, Galdass M, Karsunky H, Lohmann F, Gallagher PG, Bieker JJ. Novel role for EKLF in megakaryocyte lineage commitment. Blood 2007, 110: 3871-3880. PMID: 17715392, PMCID: PMC2190608, DOI: 10.1182/blood-2007-03-082065.Peer-Reviewed Original ResearchConceptsErythroid gene regulationKrüppel-like factorMegakaryocyte-erythroid progenitorsFormation of megakaryocytesGene regulationTranscriptional regulatorsLineage commitmentTranscription factorsHematopoietic differentiationErythroid differentiationCommon progenitorExpression profilingErythroid cellsEKLFMegakaryocyte lineageNovel roleMolecular analysisLineagesMessage levelsFunction studiesMegakaryocytesProgenitorsDifferentiationRepressionGenes
2006
Novel Role for EKLF in Megakaryocyte-Erythroid Differential Lineage Commitment.
Frontelo M, Manwani D, Galdass M, Karsunky H, Gallagher P, Bieker J. Novel Role for EKLF in Megakaryocyte-Erythroid Differential Lineage Commitment. Blood 2006, 108: 4205. DOI: 10.1182/blood.v108.11.4205.4205.Peer-Reviewed Original ResearchEKLF expressionLineage decisionsLineage commitmentErythroid gene regulationMolecular analysisFormation of megakaryocytesGene regulationTranscriptional regulatorsUnexpected functionTranscription factorsErythroid differentiationCommon progenitorExpression profilingErythroid cellsEKLFNovel rolePrecursor cellsCell compartmentMessage levelsFunction studiesMegakaryocytesRed cell compartmentCrucial roleExpressionCells
2005
A Differentiation Block in Erythroid Cells Lacking Erythroid Krupple-Like Factor (EKLF).
Gallagher P, Arcasoy M, Vayda S, Dressman H, Bieker J, Bodine D. A Differentiation Block in Erythroid Cells Lacking Erythroid Krupple-Like Factor (EKLF). Blood 2005, 106: 526. DOI: 10.1182/blood.v106.11.526.526.Peer-Reviewed Original ResearchWild typeErythroid differentiationMicroarray analysisDifferentiation blockErythroid cellsFocus genesMouse Genome 430 2.0 ArrayAffymetrix GeneChip Mouse Genome 430 2.0 ArrayFetal liver cellsCell cycle defectsTerminal erythroid differentiationCell cycle controlFetal liverIngenuity Pathway AnalysisR2 cellsMature erythroid cellsΒ-globin geneErythroid progenitor cellsErythroid genesNumerous genesDefinitive erythropoiesisDNA replicationTranscription factorsΒ-spectrinBiological functions
2004
Sequences Downstream of the Erythroid Promoter Are Required for High Level Expression of the Human α-Spectrin Gene*
Wong EY, Lin J, Forget BG, Bodine DM, Gallagher PG. Sequences Downstream of the Erythroid Promoter Are Required for High Level Expression of the Human α-Spectrin Gene*. Journal Of Biological Chemistry 2004, 279: 55024-55033. PMID: 15456760, DOI: 10.1074/jbc.m408886200.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCell DifferentiationCell MembraneCell NucleusChromatin ImmunoprecipitationCREB-Binding ProteinDeoxyribonuclease IDNADNA PrimersDNA, ComplementaryDNA-Binding ProteinsErythrocytesErythroid-Specific DNA-Binding FactorsEthidiumExonsGATA1 Transcription FactorGenes, ReporterHeLa CellsHumansImmunoprecipitationIntronsK562 CellsLuciferasesModels, GeneticMolecular Sequence DataMutationNuclear ProteinsPlasmidsPromoter Regions, GeneticSpectrinTemperatureTrans-ActivatorsTranscription FactorsTransfectionConceptsErythroid-specific expressionAlpha-spectrin geneGATA-1 sitesCore promoterDNase I hypersensitive sitesElectrophoretic mobility shift assaysChromatin immunoprecipitation assaysMobility shift assaysΑ-spectrin geneThymidine kinase promoterPositive regulatory elementHigh-level expressionGenomic orientationErythroid promoterGATA-1Membrane proteinsHypersensitive sitesImmunoprecipitation assaysRegulatory elementsSequence downstreamShift assaysErythroid differentiationTransfection assaysEnhancer activityReporter gene