2023
Erythroid Progenitor Cells in the Murine Bone Marrow: Parallels with Human Counterparts and Response to Acute Anemia
McGrath K, Kingsley P, Rust E, Schulz V, Koniski A, Schofield T, Vit L, Narla M, Blanc L, Steiner L, Gallagher P, Palis J. Erythroid Progenitor Cells in the Murine Bone Marrow: Parallels with Human Counterparts and Response to Acute Anemia. Blood 2023, 142: 2451. DOI: 10.1182/blood-2023-187741.Peer-Reviewed Original ResearchGene Ontology termsErythroid progenitor cellsErythroid progenitorsOntology termsTranscription factorsProgenitor cellsMurine erythroid progenitor cellsEPO-responsive genesMurine counterpartGlobal transcriptomic studiesLineage-specific progenitor cellsHuman erythroid progenitor cellsAnalysis of genesCholesterol homeostasisHuman counterpartLate-stage erythroid progenitorsMature red blood cellsUpregulated transcription factorsMurine erythroid progenitorsRNA-seq studiesCholesterol biosynthesis genesColony-forming progenitorsBiosynthesis genesErythroid progenitor populationsMurine bone marrowRps19 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
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
2018
MRTFA augments megakaryocyte maturation by enhancing the SRF regulatory axis
Rahman NT, Schulz VP, Wang L, Gallagher PG, Denisenko O, Gualdrini F, Esnault C, Krause DS. MRTFA augments megakaryocyte maturation by enhancing the SRF regulatory axis. Blood Advances 2018, 2: 2691-2703. PMID: 30337297, PMCID: PMC6199649, DOI: 10.1182/bloodadvances.2018019448.Peer-Reviewed Original ResearchConceptsSerum response factorHEL cellsTarget genesBinding of SRFMegakaryocyte maturationActivity of SRFSRF target genesUpregulated target genesMyocardin family proteinsTernary complex factor familyTransformation-specific proteinsPrimary hematopoietic cellsHuman erythroleukemia cell lineErythroleukemia cell lineCArG sitesPrimary human CD34Genomic sitesGenomic regionsChromatin immunoprecipitationETS factorsTranscription factorsHuman megakaryopoiesisGenomic associationsMRTFAFactor family
2013
Enhancers and Super Enhancers Are Associated With Genes That Control Phenotypic Traits In Primary Human Erythroid Cells
Schulz V, Lezon-Geyda K, Maksimova Y, Gallagher P. Enhancers and Super Enhancers Are Associated With Genes That Control Phenotypic Traits In Primary Human Erythroid Cells. Blood 2013, 122: 1200. DOI: 10.1182/blood.v122.21.1200.1200.Peer-Reviewed Original ResearchTranscriptional start siteRegulation of programsSuper enhancersErythroid cellsGene expressionErythroid enhancerTF motifsTranscription factorsHistone H3 lysine 4 monomethylationSpecific enhancersH3K27ac modificationGWAS catalogGene locusHistone H3 lysine 27 acetylationCell type-specific enhancersPrimary human erythroid cellsH3 lysine 27 acetylationAlpha-globin gene clusterDisease-associated genetic variantsGenome-wide mapsNHGRI GWAS catalogSubset of enhancersHundreds of kilobasesLysine 27 acetylationSpecialized cell typesIdentification of Biologically Relevant Enhancers in Human Erythroid Cells*
Su MY, Steiner LA, Bogardus H, Mishra T, Schulz VP, Hardison RC, Gallagher PG. Identification of Biologically Relevant Enhancers in Human Erythroid Cells*. Journal Of Biological Chemistry 2013, 288: 8433-8444. PMID: 23341446, PMCID: PMC3605659, DOI: 10.1074/jbc.m112.413260.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBasic Helix-Loop-Helix Transcription FactorsCells, CulturedChromatinChromatin ImmunoprecipitationConserved SequenceE1A-Associated p300 ProteinEnhancer Elements, GeneticErythroid CellsGATA1 Transcription FactorGene Expression RegulationGenes, ReporterHigh-Throughput Nucleotide SequencingHumansKruppel-Like Transcription FactorsLuciferases, FireflyMolecular Sequence AnnotationNF-E2 Transcription Factor, p45 SubunitOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingProto-Oncogene ProteinsRNA, MessengerSequence Analysis, DNAT-Cell Acute Lymphocytic Leukemia Protein 1TranscriptomeConceptsHuman erythroid cellsCandidate enhancersTranscriptional start siteErythroid cellsTranscription factorsGenome-wide association study catalogCell type-specific enhancersPrimary human erythroid cellsRegulation of programsGenome-wide mapsErythroid transcription factorsErythroid cell developmentSpecialized cell typesIdentification of enhancersGene expression analysisErythroid traitsMinimal conservationChromatin immunoprecipitationModerate conservationStart siteRelevant enhancersCellular developmentGenetic lociExpression analysisReporter gene
2012
Identification of Biologicaly Relevant Enhancers in Human Erythroid Cells
Su M, Steiner L, Bogardus H, Schulz V, Hardison R, Gallagher P. Identification of Biologicaly Relevant Enhancers in Human Erythroid Cells. Blood 2012, 120: 368. DOI: 10.1182/blood.v120.21.368.368.Peer-Reviewed Original ResearchTranscriptional start siteHuman erythroid cellsCell type-specific enhancersErythroid transcription factorsErythroid-specific genesTranscription factorsErythroid cellsCandidate enhancersSpecific enhancersSignificant enrichmentGene expressionPrimary human erythroid cellsRegulation of programsDisease-associated genetic variantsGenome-wide mapsHundreds of kilobasesSpecialized cell typesTranscription factor sitesKb of genesGene expression analysisParallel gene expression analysisGenomic vicinityGenomic methodologiesEvolutionary analysisHigh conservationTeleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis
Cooney JD, Hildick-Smith GJ, Shafizadeh E, McBride PF, Carroll KJ, Anderson H, Shaw GC, Tamplin OJ, Branco DS, Dalton AJ, Shah DI, Wong C, Gallagher PG, Zon LI, North TE, Paw BH. Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis. Developmental Biology 2012, 373: 431-441. PMID: 22960038, PMCID: PMC3532562, DOI: 10.1016/j.ydbio.2012.08.015.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCloning, MolecularConserved SequenceDNA-Binding ProteinsEmbryo, NonmammalianEpistasis, GeneticErythropoiesisEvolution, MolecularGene Expression Regulation, DevelopmentalHematopoiesisHematopoietic Stem CellsHematopoietic SystemModels, BiologicalMolecular Sequence DataZebrafishZebrafish ProteinsConceptsHematopoietic stem cellsTranscription factorsDefinitive hematopoiesisRUNX-1Hematopoietic stem/progenitor cell developmentKey hematopoietic transcription factorsC-MybDefinitive hematopoietic progenitorsHematopoietic transcription factorsProgenitor cell developmentLineage specificationPrimitive hematopoiesisGfi1aaEpistatic relationshipErythroid developmentTranscriptional programsGFI1BHematopoietic lineagesFunctional analysisCritical regulatorCell developmentZebrafishHematopoietic progenitorsDistinct rolesPrimitive progenitors
2011
Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation
Pilon AM, Ajay SS, Kumar SA, Steiner LA, Cherukuri PF, Wincovitch S, Anderson SM, Mullikin J, Gallagher P, Hardison R, Margulies E, Bodine D. Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation. Blood 2011, 118: e139-e148. PMID: 21900194, PMCID: PMC3208289, DOI: 10.1182/blood-2011-05-355107.Peer-Reviewed Original ResearchConceptsErythroid Kruppel-like factorKruppel-like factorChIP-seqTranscription factorsGenome-wide ChIP-seqProgenitor cellsMouse erythroid progenitor cellsCell cycle regulatory pathwaysErythroid transcription factorsGeneral cell growthRNA-seq analysisErythroid progenitor cellsTranscriptional activatorGATA factorsIntragenic regionsErythrocyte differentiationRegulatory pathwaysNuclear distributionPromoter regionParallel sequencingInteractomeDifferentiated erythroblastsCell growthTAL1Little overlap
2010
Dynamic CO-Localization of GATA1, NFE2, and EKLF and Changes in Gene Expression During Hematopoiesis
Steiner L, Schulz V, Maksimova Y, Mahajan M, Bodine D, Gallagher P. Dynamic CO-Localization of GATA1, NFE2, and EKLF and Changes in Gene Expression During Hematopoiesis. Blood 2010, 116: 741. DOI: 10.1182/blood.v116.21.741.741.Peer-Reviewed Original ResearchErythroid cellsGene expressionTranscription factorsProximal promoterCell type-specific gene expressionHuman beta-globin gene locusBeta-globin gene locusErythrocyte membrane protein genesErythroid-expressed genesGenome-wide scaleGlobin gene locusDNA-protein interactionsHuman primary erythroid cellsNF-E2Primary erythroid cellsMembrane protein geneSpecific gene expressionCritical regulatory elementsPrimary hematopoietic stemCommon regulatory siteUltrahigh-throughput sequencingLineage choiceChromatin immunoprecipitationCoordinated bindingEKLF
2009
Genome Wide Profiling of USF1 and USF2 Occupancy in Human Primary Erythroid Cells.
Steiner L, Schulz V, Maksimova Y, Tuck D, Gallagher P. Genome Wide Profiling of USF1 and USF2 Occupancy in Human Primary Erythroid Cells. Blood 2009, 114: 1456. DOI: 10.1182/blood.v114.22.1456.1456.Peer-Reviewed Original ResearchTranscription start siteLocus control regionBeta-globin locus control regionGenome-wide mapsUSF proteinsPrimary erythroid cellsBeta-globin promoterHypersensitive site 2Erythroid cellsTranscription factorsE-boxDevelopmental stage-specific genesInsulator elementsUSF bindingHelix-leucine zipper proteinBeta-globin transcriptionErythroid-expressed genesE-box consensus motifsMammalian erythroid cellsGenome-wide profilingHuman primary erythroid cellsLeucine zipper proteinCanonical E-boxMRNA transcript analysisChIP-seq experiments
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 progressionChromatin Architecture and Transcription Factor Occupancy of Erythrocyte Membrane Genes Studied by Chromatin Immunoprecipitation on Microarrays (ChIP-chip)
Steiner L, Maksimova Y, Wong C, Schulz V, Gallagher P. Chromatin Architecture and Transcription Factor Occupancy of Erythrocyte Membrane Genes Studied by Chromatin Immunoprecipitation on Microarrays (ChIP-chip). Blood 2008, 112: 2436. DOI: 10.1182/blood.v112.11.2436.2436.Peer-Reviewed Original ResearchErythrocyte membrane protein genesNF-E2 siteMembrane protein geneGATA-1 sitesTranscriptional start siteChromatin architectureTranscription factor bindingPrimary erythroid cellsGATA-1Protein geneChromatin immunoprecipitationTranscription factorsErythroid cellsH3K4me3 enrichmentFlanking DNAFactor bindingDNA sequencesK562 cellsErythroid transcription factor GATA-1Mapping protein-DNA interactionsNon-erythroid cell linesTranscription factor GATA-1Quantitative ChIP analysisTranscription factor occupancyGenome-wide scaleGenome-Wide Analysis of EKLF Occupancy in Erythroid Chromatin Reveals 5′, 3′ and Intragenic Binding Sites in EKLF Target Genes
Pilon A, Margulies E, Abaan H, Allen A, Townes T, Frederick A, Zhou D, Gallagher P, Bodine D. Genome-Wide Analysis of EKLF Occupancy in Erythroid Chromatin Reveals 5′, 3′ and Intragenic Binding Sites in EKLF Target Genes. Blood 2008, 112: 283. DOI: 10.1182/blood.v112.11.283.283.Peer-Reviewed Original ResearchCell cycle networkChIP-seqIngenuity Pathway AnalysisTranscription factorsEKLF geneWide analysisIntragenic sitesTarget genesChIP-PCRErythroid cellsMapping protein-DNA interactionsErythroid Kruppel-like factorFetal liver erythroid cellsGenome-wide scaleBeta-globin locusGenome-wide analysisCell cycle control networkProtein-DNA interactionsChIP-seq resultsTerminal erythroid maturationDNase hypersensitive sitesKnowledge of genesChIP-seq librariesChIP-seq dataFL cells
2007
Multiple Defects of Both Primitive and Definitive Erythrocytes in EKLF-Deficient Mice.
Pilon A, Beaupre J, Bieker J, Gallagher P, Bodine D. Multiple Defects of Both Primitive and Definitive Erythrocytes in EKLF-Deficient Mice. Blood 2007, 110: 1234. DOI: 10.1182/blood.v110.11.1234.1234.Peer-Reviewed Original ResearchIngenuity Pathway AnalysisFL cellsSevere anemiaFetal liver cellsG0/G1Cell cycle analysisColony-forming assaysLevels of mRNADay 14Cytometric analysisAbsolute numberLiver cellsCell cycle progressionComparable reductionMiceDifferentiation blockOrthochromatic normoblastsNormoblastsKrüppel-like factorAnemiaTranscription factorsApoptosisOsmotic fragility assaysPathway analysisWT levelsNovel 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 roleExpressionCellsDefects in E2F1/2 Expression Are Associated with Abnormalities in Cell Cycle and Differentiation in EKLF-Deficient Erythroid Cells.
Pilon A, Arcasoy M, Vayda S, Dressman H, Bieker J, Bodine D, Gallagher P. Defects in E2F1/2 Expression Are Associated with Abnormalities in Cell Cycle and Differentiation in EKLF-Deficient Erythroid Cells. Blood 2006, 108: 84. DOI: 10.1182/blood.v108.11.84.84.Peer-Reviewed Original ResearchHypersensitive sitesErythroid cellsMicroarray analysisCell cycleNumerous genesMature erythroblastsGel mobility shift assaysMicroarray dataFL cellsTranscription factor EKLFCell cycle controlMobility shift assaysΒ-globin expressionIngenuity Pathway AnalysisImmature erythroid cellsPrevious microarray analysisPrevious microarray dataE2F proteinsDefinitive erythropoiesisDNA replicationTranscription factorsColony forming assaysEKLFShift assaysTarget genesAlterations in Expression and Chromatin Configuration of the Alpha Hemoglobin-Stabilizing Protein Gene in Erythroid Krüppel-Like Factor-Deficient Mice
Pilon AM, Nilson DG, Zhou D, Sangerman J, Townes TM, Bodine DM, Gallagher PG. Alterations in Expression and Chromatin Configuration of the Alpha Hemoglobin-Stabilizing Protein Gene in Erythroid Krüppel-Like Factor-Deficient Mice. Molecular And Cellular Biology 2006, 26: 4368-4377. PMID: 16705186, PMCID: PMC1489081, DOI: 10.1128/mcb.02216-05.Peer-Reviewed Original ResearchConceptsErythroid Krüppel-like factorAlpha-hemoglobin-stabilizing proteinWild-type chromatinAHSP promoterCACCC siteBeta-globin gene transcriptionDNase I hypersensitive sitesLocal chromatin structureZinc finger proteinBeta-globin promoterKrüppel-like factorMobility shift assaysBeta-globin geneErythroid genesCACCC sequenceChromatin modulatorsFinger proteinChromatin structureSubtractive hybridizationChromatin statusCACCC boxTranscription factorsProtein geneChromatin configurationHypersensitive sites