2023
HEXIM1 is an essential transcription regulator during human erythropoiesis
Lv X, Murphy K, Murphy Z, Getman M, Rahman N, Nakamura Y, Blanc L, Gallagher P, Palis J, Mohandas N, Steiner L. HEXIM1 is an essential transcription regulator during human erythropoiesis. Blood 2023, 142: 2198-2215. PMID: 37738561, PMCID: PMC10733840, DOI: 10.1182/blood.2022019495.Peer-Reviewed Original ResearchConceptsFetal globin expressionGene expressionGlobin expressionCycle progressionErythroid gene expressionBeta-globinBeta-globin locusGenome-wide profilingRNA polymerase II activityLong non-coding RNANon-coding RNAErythroid proliferationPolymerase II activityCell cycle progressionEssential transcription regulatorRNAPII activityRNAPII occupancyGlobin locusTranscription machineryTranscription regulatorsFetal globinRNAPIIFetal gene expressionHEXIM1Human erythropoiesisPhenotypic 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
2022
HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation
Dulmovits BM, Tang Y, Papoin J, He M, Li J, Yang H, Addorisio ME, Kennedy L, Khan M, Brindley E, Ashley RJ, Ackert-Bicknell C, Hale J, Kurita R, Nakamura Y, Diamond B, Barnes BJ, Hermine O, Gallagher PG, Steiner LA, Lipton JM, Taylor N, Mohandas N, Andersson U, Al-Abed Y, Tracey KJ, Blanc L. HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation. Blood 2022, 139: 3181-3193. PMID: 35040907, PMCID: PMC9136881, DOI: 10.1182/blood.2021012048.Peer-Reviewed Original ResearchMeSH KeywordsAnemiaAnimalsErythropoiesisErythropoietinHMGB1 ProteinInflammationMiceReceptors, ErythropoietinSepsisConceptsAnemia of inflammationDamage-associated molecular pattern moleculesHigh-mobility group box 1 proteinMobility group box 1 proteinErythroid precursorsGroup box 1 proteinAdvanced glycation end productsAnti-HMGB1 antibodyGlycation end productsMolecular pattern moleculesChronic phaseSepsis onsetChronic diseasesHMGB1 receptorsAnemia developmentPattern moleculesAnemiaGenetic ablationInflammationMurine precursorRefractory stateHMGB1Reduced expansionEPO signalingDeleterious effects
2021
Regulation of RNA polymerase II activity is essential for terminal erythroid maturation
Murphy ZC, Murphy K, Myers J, Getman M, Couch T, Schulz VP, Lezon-Geyda K, Palumbo C, Yan H, Mohandas N, Gallagher PG, Steiner LA. Regulation of RNA polymerase II activity is essential for terminal erythroid maturation. Blood 2021, 138: 1740-1756. PMID: 34075391, PMCID: PMC8569412, DOI: 10.1182/blood.2020009903.Peer-Reviewed Original ResearchConceptsRNA polymerase IIRNA polymerase II activityTerminal erythroid maturationPolymerase II activityPolymerase IIErythroid maturationHuman erythroblastsGene expressionTerminal maturationII activityStage-specific regulationHistone posttranslational modificationsTransposase-accessible chromatinErythroid-specific genesAccumulation of heterochromatinHigh-throughput sequencingLevel of transcriptionLate-stage erythroblastsEssential biologic processesAccessible chromatinHistone marksTranscription elongationChromatin structureTranscriptional repressionChromatin immunoprecipitationImpairment 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 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
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 ResearchMeSH KeywordsAnimalsErythroblastsErythroid CellsErythropoiesisHumansLeukemia, Erythroblastic, AcuteMiceProteomicsConceptsTerminal 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
2019
A Unique Epigenomic Landscape Defines Human Erythropoiesis
Schulz VP, Yan H, Lezon-Geyda K, An X, Hale J, Hillyer CD, Mohandas N, Gallagher PG. A Unique Epigenomic Landscape Defines Human Erythropoiesis. Cell Reports 2019, 28: 2996-3009.e7. PMID: 31509757, PMCID: PMC6863094, DOI: 10.1016/j.celrep.2019.08.020.Peer-Reviewed Original ResearchMeSH KeywordsChromatinChromatin Assembly and DisassemblyDNA MethylationEpigenesis, GeneticErythroid CellsErythropoiesisGene Expression ProfilingGene Expression RegulationHematologic DiseasesHematopoietic Stem CellsHumansMultigene FamilyPolymorphism, Single NucleotideRegulatory Sequences, Nucleic AcidTranscriptomeConceptsChromatin accessibilityDNA methylationHuman erythropoiesisStage-specific gene regulationErythroid cellsPrimary human erythroid cellsChromatin state dynamicsCell typesCis-regulatory elementsGenome-wide studiesSpecialized cell typesHuman erythroid cellsCell phenotypic variationNonhematopoietic cell typesChromatin primingErythroid genesEpigenomic landscapeGene regulationMammalian erythropoiesisPhenotypic variationTranscriptome dataOrganismal needsRegulation of erythropoiesisNonpromoter sitesGene expressionIdentification and transcriptome analysis of erythroblastic island macrophages
Li W, Wang Y, Zhao H, Zhang H, Xu Y, Wang S, Guo X, Huang Y, Zhang S, Han Y, Wu X, Rice CM, Huang G, Gallagher PG, Mendelson A, Yazdanbakhsh K, Liu J, Chen L, An X. Identification and transcriptome analysis of erythroblastic island macrophages. Blood 2019, 134: 480-491. PMID: 31101625, PMCID: PMC6676133, DOI: 10.1182/blood.2019000430.Peer-Reviewed Original ResearchConceptsErythroblastic islandsEBI macrophagesErythroid cellsErythroblastic island macrophagesGene expression profilesTranscriptome analysisNonerythroid cellsMacrophage functionHematopoietic nicheExpression profilesSpecialized functionsCentral macrophageKnockin mouse modelFlow cytometry analysisEpoRKey moleculesIron recyclingBone marrowCytometry analysisFetal liverNicheEfficient erythropoiesisErythropoiesisIron sourceImportant resource
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
2016
CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells
Steiner LA, Schulz V, Makismova Y, Lezon-Geyda K, Gallagher PG. CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells. PLOS ONE 2016, 11: e0155378. PMID: 27219007, PMCID: PMC4878738, DOI: 10.1371/journal.pone.0155378.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCCCTC-Binding FactorCells, CulturedChromatinChromatin ImmunoprecipitationErythroid CellsErythropoiesisGene Expression ProfilingHematopoietic Stem CellsHigh-Throughput Nucleotide SequencingHumansK562 CellsNuclear ProteinsPromoter Regions, GeneticProtein BindingProtein Interaction MapsRepressor ProteinsSequence Analysis, RNAConceptsPrimary human erythroid cellsRepressive chromatin domainsHuman erythroid cellsChromatin domainsErythroid cellsChromatin architectureGene promoterGene expressionPrimary human hematopoietic stemCell type-specific mannerCritical cellular processesSites of CTCFGenome-wide dataHigh-throughput sequencingMRNA transcriptome analysisHuman hematopoietic stemRepressive chromatinCohesin sitesProtein occupancyInsulator functionRepressive domainsTranscriptional regulationCTCF sitesDomain architectureRelated gene expressionSetd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation
Li Y, Schulz VP, Deng C, Li G, Shen Y, Tusi BK, Ma G, Stees J, Qiu Y, Steiner LA, Zhou L, Zhao K, Bungert J, Gallagher PG, Huang S. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic Acids Research 2016, 44: 7173-7188. PMID: 27141965, PMCID: PMC5009724, DOI: 10.1093/nar/gkw327.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NuclearCell LineageCells, CulturedChromatinChromatin Assembly and DisassemblyChromatin ImmunoprecipitationErythroblastsErythrocyte CountErythrocytesErythropoiesisFemaleGene Expression RegulationHemoglobinsHistone-Lysine N-MethyltransferaseHistonesHumansLysineMaleMethylationMiceMice, KnockoutMicrococcal NucleaseMultiprotein ComplexesNerve Tissue ProteinsPromoter Regions, GeneticSpleenTranscription FactorsUpstream Stimulatory FactorsConceptsNURF complexChromatin dynamicsErythroid genesLineage commitmentAdult β-globin geneErythroid gene promotersErythroid lineage differentiationCell context-dependent mannerErythroid lineage commitmentChromatin structural alterationsContext-dependent mannerΒ-globin geneChromatin architectureEnhancer accessibilityChromatin accessibilityNucleosome repositioningTranscription regulationChromatin structureH3K4 methylationGene regulationComplex occupancyMammalian cellsGene activationGene transcriptionLineage differentiation
2015
Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors
Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, Al-Abed Y, Didier S, Gould M, Husain-Krautter S, Singh SA, Chan KW, Vlachos A, Allen SL, Taylor N, Marambaud P, An X, Gallagher PG, Mohandas N, Lipton JM, Liu JM, Blanc L. Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors. Blood 2015, 127: 1481-1492. PMID: 26679864, PMCID: PMC4797024, DOI: 10.1182/blood-2015-09-667923.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnemia, Sickle CellBeta-GlobinsCarrier ProteinsErythroid Precursor CellsErythropoiesisFetal HemoglobinGamma-GlobinsGene Expression Regulation, DevelopmentalGenetic VectorsHematopoietic Stem CellsHistone DemethylasesHumansIkaros Transcription FactorKruppel-Like Transcription FactorsLentivirusMultiple MyelomaNeoplasm ProteinsNuclear ProteinsProteasome Endopeptidase ComplexRepressor ProteinsRNA InterferenceRNA, Small InterferingSOXD Transcription FactorsThalidomideTranscription, GeneticConceptsSickle cell anemiaCell anemiaΓ-globinThird-generation immunomodulatory drugAdult human erythroblastsMultiple myeloma patientsHematopoietic progenitorsΓ-globin levelsΓ-globin repressionCurrent therapeutic strategiesErythroid differentiation programFetal hemoglobinAdult hematopoietic progenitorsPomalidomide treatmentImmunomodulatory drugsMyeloma patientsTranscriptional reprogrammingFetal hemoglobin productionTranscription networksTherapeutic strategiesDifferentiation programPomalidomideHuman erythroblastsΒ-hemoglobinopathiesGenetic ablationHuman 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
Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E
Li J, Hale J, Bhagia P, Xue F, Chen L, Jaffray J, Yan H, Lane J, Gallagher PG, Mohandas N, Liu J, An X. Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E. Blood 2014, 124: 3636-3645. PMID: 25339359, PMCID: PMC4256913, DOI: 10.1182/blood-2014-07-588806.Peer-Reviewed Original ResearchConceptsHuman BFUProgenitor populationsErythroid progenitorsDistinct progenitor populationsColony-forming unit-erythroid (CFU-E) cellsCFU-E cellsCFU-E coloniesCFU-E progenitorsHuman erythroid progenitorsUnit erythroid cellsColony assayErythroid cell culturesErythroid progenitor populationsTranscriptome analysisUnique transcriptomeStem cell factorCell culturesBioinformatics analysisHuman erythropoiesisFlow cytometry-based strategyMolecular characterizationBFU-E coloniesDifferentiation stagePrimary cellsCell factorGlobal 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
2012
Teleost 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 overlapSingle-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo
Isern J, He Z, Fraser ST, Nowotschin S, Ferrer-Vaquer A, Moore R, Hadjantonakis AK, Schulz V, Tuck D, Gallagher PG, Baron MH. Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo. Blood 2011, 117: 4924-4934. PMID: 21263157, PMCID: PMC3100699, DOI: 10.1182/blood-2010-10-313676.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineageCytokinesDNA PrimersEpsilon-GlobinsErythroid Precursor CellsErythropoiesisFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksGlycolysisGreen Fluorescent ProteinsGrowth SubstancesMaleMiceMice, Inbred ICRMice, TransgenicOxygenPregnancyRecombinant Fusion ProteinsRNA, MessengerSignal TransductionConceptsPrimitive erythroid progenitorsMouse embryosErythroid progenitorsGlobal expression profilesEmbryonic day 7.5Critical regulatory factorKey regulatory pathwaysOnset of circulationFirst transcriptomeRemarkable proliferative capacityTranscript diversityTransgenic reporterTranscriptome analysisFirst cell typeRegulatory pathwaysHematopoietic lineagesExpression profilesRegulatory factorsCell typesDay 7.5EmbryosProgenitorsYolk sacBlood progenitorsGlycolytic profile