2023
Integrative 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 Framework
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 factorsGenome-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 mechanismsMicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells
Browne G, Dragon J, Hong D, Messier T, Gordon J, Farina N, Boyd J, VanOudenhove J, Perez A, Zaidi S, Stein J, Stein G, Lian J. MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells. Tumor Biology 2016, 37: 8825-8839. PMID: 26749280, PMCID: PMC4939137, DOI: 10.1007/s13277-015-4710-6.Peer-Reviewed Original ResearchConceptsMDA-MB-231 cellsBreast cancer progressionMiR-378Breast cancer cellsCancer progressionMMTV-PyMT transgenic mouse modelCancer cellsLuciferase reporter assaysMiRNA replacement therapyMDA-MB-231 human breast cancer cellsBreast cancerTranscription factorsNumerous miRNAsEctopic expressionRegulatory pathwaysUntranslated regionMicroarray profilingReporter assaysHuman breast cancer cellsTriple-negative MDA-MB-231Breast cancer cell line MCF7Human breast cancer cell line MCF7Cell migrationRUNX1 expressionNormal hematopoiesis
2011
PSA regulates androgen receptor expression in prostate cancer cells
Saxena P, Trerotola M, Wang T, Li J, Sayeed A, VanOudenhove J, Adams D, FitzGerald T, Altieri D, Languino L. PSA regulates androgen receptor expression in prostate cancer cells. The Prostate 2011, 72: 769-776. PMID: 21956655, PMCID: PMC3404455, DOI: 10.1002/pros.21482.Peer-Reviewed Original ResearchConceptsProstate-specific antigenAndrogen receptorC4-2B cellsShort hairpin RNAPrCa cellsAndrogen-independent cell linesAndrogen receptor expressionProtein levelsAR transcriptional activityAR protein levelsAR mRNA levelsProstate cancer progressionProstate cancer cellsTransient siRNA knockdownStable short hairpin RNAAR activatorsPSA levelsAR expressionEffect of downregulationPhosphorylation of SrcSerum biomarkersAR mRNAReceptor expressionAR levelsReal-time PCR
2009
Analysis of PKR Structure by Small-Angle Scattering
VanOudenhove J, Anderson E, Krueger S, Cole J. Analysis of PKR Structure by Small-Angle Scattering. Journal Of Molecular Biology 2009, 387: 910-920. PMID: 19232355, PMCID: PMC2663012, DOI: 10.1016/j.jmb.2009.02.019.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBinding SitesDimerizationEIF-2 KinaseHumansImmunity, InnateModels, MolecularMolecular Sequence DataProtein ConformationProtein Structure, QuaternaryProtein Structure, TertiaryRNA, Double-StrandedScattering, Small AngleSequence Homology, Amino AcidX-Ray DiffractionConceptsProtein kinase RDouble-stranded RNATandem double-stranded RNAC-terminal kinase domainN-terminal double-stranded RNAFamily of proteinsInterdomain linker regionAntiviral defense pathwayDefense pathwaysAutophosphorylation reactionKinase domainRNA activatorUnstructured regionsLinker regionFlexible linkerRNAExtended conformationSmall-angle X-ray scatteringDiverse structuresGuinier analysisDistance distribution functionConformationKinaseKey componentX-ray scattering