2023
Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways
Papoin J, Yan H, Leduc M, Le Gall M, Narla A, Palis J, Steiner L, Gallagher P, Hillyer C, Gautier E, Mohandas N, Blanc L. Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways. American Journal Of Hematology 2023, 99: 99-112. PMID: 37929634, PMCID: PMC10877306, DOI: 10.1002/ajh.27145.Peer-Reviewed Original ResearchConceptsErythroid progenitor differentiationCell cycleErythroid progenitorsProgenitor differentiationMass spectrometry-based proteomicsFurther functional analysisSpectrometry-based proteomicsHuman erythroid progenitorsProtein machineryErythroid progenitor proliferationTerminal erythropoiesisProteomic characterizationHematopoietic stem cellsProteomic dataProgenitor populationsHuman erythropoiesisReticulocyte maturationFunctional analysisErythroid lineageOxidative phosphorylationProgenitor proliferationErythroid disordersMetabolic pathwaysAbsolute expressionStem cells
2021
An 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 ResearchMeSH KeywordsAscorbic AcidCell DifferentiationErythropoiesisHumansIsocitrate DehydrogenaseMitochondriaConceptsIsocitrate 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
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
2017
STAT4 and T-bet control follicular helper T cell development in viral infections
Weinstein JS, Laidlaw BJ, Lu Y, Wang JK, Schulz VP, Li N, Herman EI, Kaech SM, Gallagher PG, Craft J. STAT4 and T-bet control follicular helper T cell development in viral infections. Journal Of Experimental Medicine 2017, 215: 337-355. PMID: 29212666, PMCID: PMC5748849, DOI: 10.1084/jem.20170457.Peer-Reviewed Original ResearchConceptsIL-21Tfh cellsT-betViral infectionFollicular helper T cellsHelper T cell developmentAcute viral infectionIFN-γ productionHelper T cellsGerminal center B cell survivalB cell survivalT cell developmentIL-4Viral challengeIL-9T cellsImmunoglobulin isotypesIFNSoluble factorsGC responseInfectionGC reactionSTAT4BCL6Cell survival
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
Global 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 analysisNonstochastic 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
USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription
Deng C, Li Y, Liang S, Cui K, Salz T, Yang H, Tang Z, Gallagher PG, Qiu Y, Roeder R, Zhao K, Bungert J, Huang S. USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription. PLOS Genetics 2013, 9: e1003524. PMID: 23754954, PMCID: PMC3675019, DOI: 10.1371/journal.pgen.1003524.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsCell DifferentiationCell LineageEmbryonic Stem CellsEpigenesis, GeneticGene Expression RegulationHistone-Lysine N-MethyltransferaseHomeodomain ProteinsHumansK562 CellsMesodermMethyltransferasesProto-Oncogene ProteinsT-Cell Acute Lymphocytic Leukemia Protein 1Transcription FactorsTranscriptional ActivationUpstream Stimulatory FactorsConceptsEmbryonic stem cellsLineage differentiationTrithorax complexesHoxb4 genesMethyltransferase complexTranscription preinitiation complex assemblyHistone H3K4 methyltransferase complexRNA interference-mediated knockdownBivalent chromatin domainsH3K4 methyltransferase complexUndifferentiated embryonic stem cellsPreinitiation complex assemblyHistone methyltransferase complexTranscription factor USF1H3K4 methyltransferase activityHematopoietic stem/progenitor cellsHematopoietic cell populationsStem/progenitor cellsDPY-30HOXB4 promoterMesoderm specificationChromatin domainsMesoderm differentiationH3K4me3 modificationHematopoietic transition
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
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