2024
Clonal hematopoiesis of indeterminate potential is associated with increased risk of immune checkpoint inhibitor myocarditis in a prospective study of a cardio-oncology cohort
Jaber Chehayeb R, Singh J, Matute-Martinez C, Chen N, Guajardo A, Lin D, Jayakrishnan R, Christofides A, Leveille E, Im Y, Biancon G, VanOudenhove J, Ibrahim E, Ardasheva A, Jha A, Hwa J, Halene S, Kwan J. Clonal hematopoiesis of indeterminate potential is associated with increased risk of immune checkpoint inhibitor myocarditis in a prospective study of a cardio-oncology cohort. Cardio-Oncology 2024, 10: 84. PMID: 39587635, PMCID: PMC11590368, DOI: 10.1186/s40959-024-00289-z.Peer-Reviewed Original ResearchImmune checkpoint inhibitor myocarditisImmune checkpoint inhibitorsImmune checkpoint inhibitor useICI-myocarditisIndeterminate potentialProspective studyImmune checkpoint inhibitor therapyCancer therapyClonal hematopoiesis of indeterminate potentialCancer treated with immunotherapyIncreased T cell activationObstructive coronary artery diseaseMultivariate competing risk analysisCardiotoxic cancer therapyRisks Cox regressionAssociated with increased riskIncreased all-cause mortalityPatient co-morbiditiesRisk of cardiomyopathyT cell activationCompeting risk analysisCoronary artery calcificationCoronary artery diseaseAll-cause mortalityHeart failure patientsGPR68 supports AML cells through the calcium/calcineurin pro-survival pathway and confers chemoresistance by mediating glucose metabolic symbiosis
He X, Hawkins C, Lawley L, Phan T, Park I, Joven N, Zhang J, Wunderlich M, Mizukawa B, Pei S, Patel A, VanOudenhove J, Halene S, Fang J. GPR68 supports AML cells through the calcium/calcineurin pro-survival pathway and confers chemoresistance by mediating glucose metabolic symbiosis. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2024, 167565. PMID: 39522891, DOI: 10.1016/j.bbadis.2024.167565.Peer-Reviewed Original ResearchAcute myeloid leukemiaAcute myeloid leukemia cellsPro-survival pathwaysInhibiting isocitrate dehydrogenaseMetabolic symbiosisMyelodysplastic syndromeHematopoietic malignanciesExtracellular acidosisAssociated with inferior clinical outcomesCellular respirationFirst-line chemotherapeutic agentAcute myeloid leukemia patientsInferior clinical outcomesAerobic glycolysisCell survival in vitroEngraftment in vivoDecreased Ca<sup>2+</sup> levelDecreased aerobic glycolysisSurvival in vitroGlucose metabolic pathwaysG protein-coupled receptor 68Impacts chemosensitivityIn vitro observationsTumoricidal effectMyeloid leukemiaAplastic anemia in association with multiple myeloma: clinical and pathophysiological insights
Muradashvili T, Liu Y, VanOudenhove J, Gu S, Krause D, Montanari F, Carlino M, Mancuso R, Stempel J, Halene S, Zeidan A, Podoltsev N, Neparidze N. Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights. Leukemia & Lymphoma 2024, ahead-of-print: 1-8. PMID: 39225418, DOI: 10.1080/10428194.2024.2393260.Peer-Reviewed Original ResearchAplastic anemiaMultiple myelomaImmunosuppressive therapyTransfusion requirementsProgenitor cellsPlasma cell-directed therapyT-cell destructionCell-directed therapiesInhibition of erythroid colony formationErythroid colony formationLevels of IL8Severe AAImmune cytopeniasPartial responseMM patientsHematopoietic stemSerum testsPartial improvementPathophysiological insightsPatientsImmune systemPlatelet apoptosisCytopeniasColony formationMyelomaClonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy
Leveille E, Cheheyeb R, Matute-Martinez C, Chen N, Jayakrishnan R, Christofides A, Lin D, Im Y, Biancon G, VanOudenhove J, Halene S, Kwan J. Clonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy. JACC CardioOncology 2024, 6: 605-607. PMID: 39239339, PMCID: PMC11372300, DOI: 10.1016/j.jaccao.2024.05.013.Peer-Reviewed Original Research
2023
CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS)
Kewan T, Mirza S, Pine A, Rasheed Y, Hamouche R, Leveille E, Goshua G, Gu S, Liu Y, Vanoudenhove J, Bar N, Neparidze N, Foss F, Gowda L, Isufi I, Halene S, Lee A, Seropian S. CAR T-Related Toxicities Based on Dynamic Proteomic Profiles Identifies Risk Factors for Cytokine Release Syndrome (CRS) and Immune Effector Cell -Associated Neurotoxicity Syndrome (ICANS). Blood 2023, 142: 2132. DOI: 10.1182/blood-2023-187295.Peer-Reviewed Original ResearchCytokine release syndromeDiffuse large B-cell lymphomaCAR T-cell therapyCAR T-cell productsCAR-T productsNon-Hodgkin lymphomaBest cutoff pointMultiple myelomaHigher oddsDay 3Risk factorsTime pointsCutoff pointDay 5Day 0Median absolute lymphocyte countChimeric antigen receptor T cellsRefractory non-Hodgkin lymphomaCAR T-cell infusionAntigen receptor T cellsLarge B-cell lymphomaCAR-T activationFludarabine/cyclophosphamideHigher baseline CRPPossible inflammatory mediatorsImpact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant.
VanOudenhove J, Liu Y, Nelakanti R, Kim D, Busarello E, Ovalle NT, Qi Z, Mamillapalli P, Siddon A, Bai Z, Axtmayer A, Corso C, Kothari S, Foss F, Isufi I, Tebaldi T, Gowda L, Fan R, Seropian S, Halene S. Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant. BioRxiv 2023 PMID: 37961434, DOI: 10.1101/2023.10.26.564259.Peer-Reviewed Original Research In PressMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023)
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023). Small Methods 2023, 7 DOI: 10.1002/smtd.202370057.Peer-Reviewed Original ResearchIntegrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes
Yankee T, Oh S, Winchester E, Wilderman A, Robinson K, Gordon T, Rosenfeld J, VanOudenhove J, Scott D, Leslie E, Cotney J. Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes. Nature Communications 2023, 14: 4623. PMID: 37532691, PMCID: PMC10397224, DOI: 10.1038/s41467-023-40363-1.Peer-Reviewed Original ResearchConceptsGene co-expression analysisSingle-cell RNA-seqCraniofacial disordersSet of genesCo-expression analysisTranscriptome dynamicsDevelopmental enhancersRegulatory hubEpigenomic dataCraniofacial developmentRNA-seqDe novo mutationsDisease genesGene expressionIntegrative analysisCraniofacial tissuesGenesNovo mutationsHuman tissuesMutationsDevelopment identifiesCommon congenital defectsWeeks post conceptionPost conceptionCraniofacial region
2022
Is it the time to integrate novel sequencing technologies into clinical practice?
VanOudenhove J, Halene S, Mendez L. Is it the time to integrate novel sequencing technologies into clinical practice? Current Opinion In Hematology 2022, 30: 70-77. PMID: 36602939, DOI: 10.1097/moh.0000000000000754.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNovel sequencing technologiesSequencing technologiesUnprecedented biological insightsNext-generation sequencing techniquesDNA sequencing technologiesHigh-throughput NGSRare cell populationsBiological insightsMultiomics approachSequencing techniquesGenotype-phenotype correlationClonal diversityCellular resolutionMechanistic insightsCell populationsPhenotype correlationMyeloid diseasesClonesClonal hierarchyClonal haematopoiesisResidual clonesInsightsSeqDiversityImproved captureNIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health
Lee P, Benz C, Blood P, Börner K, Campisi J, Chen F, Daldrup-Link H, De Jager P, Ding L, Duncan F, Eickelberg O, Fan R, Finkel T, Furman D, Garovic V, Gehlenborg N, Glass C, Heckenbach I, Joseph Z, Katiyar P, Kim S, Königshoff M, Kuchel G, Lee H, Lee J, Ma J, Ma Q, Melov S, Metis K, Mora A, Musi N, Neretti N, Passos J, Rahman I, Rivera-Mulia J, Robson P, Rojas M, Roy A, Scheibye-Knudsen M, Schilling B, Shi P, Silverstein J, Suryadevara V, Xie J, Wang J, Wong A, Niedernhofer L, Wang S, Anvari H, Balough J, Benz C, Bons J, Brenerman B, Evans W, Gerencser A, Gregory H, Hansen M, Justice J, Kapahi P, Murad N, O’Broin A, Pavone M, Powell M, Scott G, Shanes E, Shankaran M, Verdin E, Winer D, Wu F, Adams A, Blood P, Bueckle A, Cao-Berg I, Chen H, Davis M, Filus S, Hao Y, Hartman A, Hasanaj E, Helfer J, Herr B, Joseph Z, Molla G, Mou G, Puerto J, Quardokus E, Ropelewski A, Ruffalo M, Satija R, Schwenk M, Scibek R, Shirey W, Sibilla M, Welling J, Yuan Z, Bonneau R, Christiano A, Izar B, Menon V, Owens D, Phatnani H, Smith C, Suh Y, Teich A, Bekker V, Chan C, Coutavas E, Hartwig M, Ji Z, Nixon A, Dou Z, Rajagopal J, Slavov N, Holmes D, Jurk D, Kirkland J, Lagnado A, Tchkonia T, Abraham K, Dibattista A, Fridell Y, Howcroft T, Jhappan C, Montes V, Prabhudas M, Resat H, Taylor V, Kumar M, Suryadevara V, Cigarroa F, Cohn R, Cortes T, Courtois E, Chuang J, Davé M, Domanskyi S, Enninga E, Eryilmaz G, Espinoza S, Gelfond J, Kirkland J, Kuchel G, Kuo C, Lehman J, Aguayo-Mazzucato C, Meves A, Rani M, Sanders S, Thibodeau A, Tullius S, Ucar D, White B, Wu Q, Xu M, Yamaguchi S, Assarzadegan N, Cho C, Hwang I, Hwang Y, Xi J, Adeyi O, Aliferis C, Bartolomucci A, Dong X, DuFresne-To M, Ikramuddin S, Johnson S, Nelson A, Niedernhofer L, Revelo X, Trevilla-Garcia C, Sedivy J, Thompson E, Robbins P, Wang J, Aird K, Alder J, Beaulieu D, Bueno M, Calyeca J, Chamucero-Millaris J, Chan S, Chung D, Corbett A, Gorbunova V, Gowdy K, Gurkar A, Horowitz J, Hu Q, Kaur G, Khaliullin T, Lafyatis R, Lanna S, Li D, Ma A, Morris A, Muthumalage T, Peters V, Pryhuber G, Reader B, Rosas L, Sembrat J, Shaikh S, Shi H, Stacey S, Croix C, Wang C, Wang Q, Watts A, Gu L, Lin Y, Rabinovitch P, Sweetwyne M, Artyomov M, Ballentine S, Chheda M, Davies S, DiPersio J, Fields R, Fitzpatrick J, Fulton R, Imai S, Jain S, Ju T, Kushnir V, Link D, Ben Major M, Oh S, Rapp D, Rettig M, Stewart S, Veis D, Vij K, Wendl M, Wyczalkowski M, Craft J, Enninful A, Farzad N, Gershkovich P, Halene S, Kluger Y, VanOudenhove J, Xu M, Yang J, Yang M. NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nature Aging 2022, 2: 1090-1100. PMID: 36936385, PMCID: PMC10019484, DOI: 10.1038/s43587-022-00326-5.Peer-Reviewed Original ResearchConceptsSenescence-associated secretory phenotypeSenescent cellsSecretory phenotypeMulti-omics datasetsStable growth arrestHuman lifespanDiverse rolesGrowth arrestProinflammatory senescence-associated secretory phenotypeHuman tissuesPhenotypeMetabolic changesCellsHuman healthLifespanPhysiological healthCommon Coordinate FrameworkZebrafish models of Alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye
Yoon B, Yeung P, Santistevan N, Bluhm L, Kawasaki K, Kueper J, Dubielzig R, Vanoudenhove J, Cotney J, Liao E, Grinblat Y. Zebrafish models of Alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye. Biology Open 2022, 11: bio059189. PMID: 35142342, PMCID: PMC9167625, DOI: 10.1242/bio.059189.Peer-Reviewed Original ResearchConceptsALX geneAnterior neurocraniumZebrafish modelGenetic mechanismsNovel roleAnterior segment formationHomeobox transcription factorCranial neural crestOxidative stress responseParalogous genesConserved roleAnterior segment defectsAbsence of eyesEthanol toxicityTranscription factorsTranscriptomic analysisLineage labelingAlx1Midfacial morphogenesisKey regulatorNeural crestStress responseSegment formationMutantsVascular developmentMission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies
Figueiredo JC, Hirsch FR, Kushi LH, Nembhard WN, Crawford JM, Mantis N, Finster L, Merin NM, Merchant A, Reckamp KL, Melmed GY, Braun J, McGovern D, Parekh S, Corley DA, Zohoori N, Amick BC, Du R, Gregersen PK, Diamond B, Taioli E, Sariol C, Espino A, Weiskopf D, Gifoni A, Brien J, Hanege W, Lipsitch M, Zidar DA, McAlearney A, Wajnberg A, LaBaer J, Lewis E, Binder RA, Moormann AM, Forconi C, Forrester S, Batista J, Schieffelin J, Kim D, Biancon G, VanOudenhove J, Halene S, Fan R, Barouch DH, Alter G, Pinninti S, Boppana SB, Pati SK, Latting M, Karaba AH, Roback J, Sekaly R, Neish A, Brincks AM, Granger DA, Karger AB, Thyagarajan B, Thomas SN, Klein SL, Cox AL, Lucas T, Furr-Holden D, Key K, Jones N, Wrammerr J, Suthar M, Wong S, Bowman NM, Simon V, Richardson LD, McBride R, Krammer F, Rana M, Kennedy J, Boehme K, Forrest C, Granger SW, Heaney CD, Lapinski M, Wallet S, Baric RS, Schifanella L, Lopez M, Fernández S, Kenah E, Panchal AR, Britt WJ, Sanz I, Dhodapkar M, Ahmed R, Bartelt LA, Markmann AJ, Lin JT, Hagan RS, Wolfgang MC, Skarbinski J. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies. Open Forum Infectious Diseases 2022, 9: ofac171. PMID: 35765315, PMCID: PMC9129196, DOI: 10.1093/ofid/ofac171.Peer-Reviewed Original ResearchCoronavirus disease 2019Disease 2019Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Healthy pregnant womenInflammatory bowel diseaseLong-term sequelaeHuman immunodeficiency virusSyndrome coronavirus 2Epidemiologic cohort studiesNational Cancer InstituteTransplant recipientsCohort studyBowel diseaseClinical outcomesImmunodeficiency virusPregnant womenAutoimmune diseasesCoronavirus 2Risk factorsCardiovascular diseaseTreatment strategiesImmune responseCancer Institute
2021
Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment
Pettinato A, Yoo D, VanOudenhove J, Chen Y, Cohn R, Ladha F, Yang X, Thakar K, Romano R, Legere N, Meredith E, Robson P, Regnier M, Cotney J, Murry C, Hinson J. Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment. Cell Reports 2021, 35: 109088. PMID: 33951429, PMCID: PMC8161465, DOI: 10.1016/j.celrep.2021.109088.Peer-Reviewed Original ResearchConceptsCell cycle arrestSarcomere functionHuman cardiomyocyte modelHuman cardiac regenerationInfarcted rat heartsCardiomyocyte engraftmentCell engraftmentReplicative rateRat heartDNA damage responseCardiomyocyte modelCardiac regenerationOxidative metabolismUnclear mechanismsProgressive polyploidizationCyclin B1P53-dependent DNA damage responseEngraftmentP53 activationArrestDamage responseSingle-cell transcriptomicsReplicative arrest
2020
Epigenomic and Transcriptomic Dynamics During Human Heart Organogenesis
VanOudenhove J, Yankee T, Wilderman A, Cotney J. Epigenomic and Transcriptomic Dynamics During Human Heart Organogenesis. Circulation Research 2020, 127: e184-e209. PMID: 32772801, PMCID: PMC7554226, DOI: 10.1161/circresaha.120.316704.Peer-Reviewed Original ResearchMeSH KeywordsChromatinEnhancer Elements, GeneticEpigenomicsGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenetic VariationHeartHeart Defects, CongenitalHistone CodeHomeobox Protein Nkx-2.5HumansNAV1.5 Voltage-Gated Sodium ChannelOrganogenesisRegulatory Sequences, Ribonucleic AcidT-Box Domain ProteinsTranscriptomeConceptsRegulatory sequencesHeart enhancersHeart organogenesisGene expression network analysisWeighted gene coexpression networkGene expression dynamicsGene expression networksPutative disease genesWhole-genome sequencing dataGene coexpression networksExpression network analysisDisease-relevant genesGenome sequencing dataRare sequence alterationsHeart-specific expressionClear genetic componentChromatin stateTranscriptomic dynamicsHistone modificationsFunctional annotationExpression networksExpression dynamicsGene modulesCoexpression networkGenetic variation
2018
High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development
Wilderman A, VanOudenhove J, Kron J, Noonan JP, Cotney J. High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development. Cell Reports 2018, 23: 1581-1597. PMID: 29719267, PMCID: PMC5965702, DOI: 10.1016/j.celrep.2018.03.129.Peer-Reviewed Original ResearchConceptsRegulatory sequencesEmbryonic developmentEmbryonic craniofacial developmentEmbryonic craniofacial tissueGene regulatory programsNormal facial variationHuman embryonic developmentCraniofacial abnormalitiesEpigenomic annotationsEpigenomic atlasCraniofacial developmentIntronic sequencesCraniofacial tissuesRegulatory programsCraniofacial researchersMultiple tissuesCell typesSignificant enrichmentSystematic identificationCommon variantsCausal regionOrofacial cleftingEmbryonic periodSequenceCraniofacial complex
2017
Unique Regulatory Mechanisms for the Human Embryonic Stem Cell Cycle
VanOudenhove J, Grandy R, Ghule P, Lian J, Stein J, Zaidi S, Stein G. Unique Regulatory Mechanisms for the Human Embryonic Stem Cell Cycle. Journal Of Cellular Physiology 2017, 232: 1254-1257. PMID: 27532275, PMCID: PMC5315681, DOI: 10.1002/jcp.25567.Peer-Reviewed Original ResearchConceptsCell cyclePluripotent human embryonic stem cellsPluripotent cell cyclePluripotent cell populationHuman embryonic stem cellsEmbryonic stem cellsG1 periodCell cycle pauseMesodermal lineage cellsEpigenetic mechanismsEctodermal differentiationRegulatory eventsUnrestricted proliferationLineage cellsStem cellsCell populationsUnique mechanismRecent findingsDifferentiationPluripotencyCellsMechanismProliferationCyclePrecocious Phenotypic Transcription‐Factor Expression During Early Development
VanOudenhove J, Medina R, Ghule P, Lian J, Stein J, Zaidi S, Stein G. Precocious Phenotypic Transcription‐Factor Expression During Early Development. Journal Of Cellular Biochemistry 2017, 118: 953-958. PMID: 27591551, PMCID: PMC5336526, DOI: 10.1002/jcb.25723.Peer-Reviewed Original ResearchConceptsPhenotypic transcription factorsTranscription factorsPrecocious expressionRUNX1 transcription factorTranscriptional controlLineage identityGene expressionNovel roleBiological importanceMesenchymal transitionEarly differentiationMesenchymal differentiationTransient upregulationDetailed mechanistic studiesExpressionDifferentiationMechanistic studiesRUNX1RoleUpregulationFurther studies
2016
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
VanOudenhove J, Medina R, Ghule P, Lian J, Stein J, Zaidi S, Stein G. Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling. Stem Cell Reports 2016, 7: 884-896. PMID: 27720906, PMCID: PMC5106514, DOI: 10.1016/j.stemcr.2016.09.006.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsHESC differentiationMesendodermal lineage commitmentPhenotypic transcription factorsLoss of repressionRUNX1 depletionMesenchymal transitionEmbryonic stem cellsLoss of RUNX1Mesendodermal lineagesMesendodermal differentiationLineage commitmentTranscription factorsBiochemical approachesEpithelial genesCell motilityFunctional analysisEpithelial marker expressionRUNX1 expressionStem cellsRUNX1TGFB2DifferentiationEarly eventsCandidate factorsLineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.
Van Oudenhove JJ, Grandy RA, Ghule PN, Del Rio R, Lian JB, Stein JL, Zaidi SK, Stein GS. Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause. Stem Cells 2016, 34: 1765-75. PMID: 26946228, DOI: 10.1002/stem.2352.Peer-Reviewed Original ResearchGenome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation
Grandy R, Whitfield T, Wu H, Fitzgerald M, VanOudenhove J, Zaidi S, Montecino M, Lian J, van Wijnen A, Stein J, Stein G. Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation. Molecular And Cellular Biology 2016, 36: 615-627. PMID: 26644406, PMCID: PMC4751694, DOI: 10.1128/mcb.00877-15.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell DifferentiationCell LineChromatinDNA MethylationDNA-Binding ProteinsEpigenesis, GeneticGene Expression Regulation, DevelopmentalGenome-Wide Association StudyHistone-Lysine N-MethyltransferaseHistonesHuman Embryonic Stem CellsHumansMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsConceptsHuman embryonic stem cellsBivalent genesHistone modificationsCell cycleCell cycle-dependent fashionPluripotent cell cycleRepressive histone modificationsPosttranslational histone modificationsH3K4me3/H3K27me3Maintenance of pluripotencyHistone modification signaturesMethylation/demethylationLevels of H3K4me3Embryonic stem cellsInduction of differentiationChromatin regulationChromatin modifiersEpigenetic landscapeCell identityModification signaturesLineage commitmentGenomic enrichmentGene promoterProgeny cellsMolecular mechanisms