2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformations
2019
The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
Belair C, Sim S, Kim KY, Tanaka Y, Park IH, and, Wolin SL. The RNA exosome nuclease complex regulates human embryonic stem cell differentiation. Journal Of Cell Biology 2019, 218: 2564-2582. PMID: 31308215, PMCID: PMC6683745, DOI: 10.1083/jcb.201811148.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCross-Linking ReagentsEndodermExosome Multienzyme Ribonuclease ComplexForkhead Transcription FactorsGene Expression RegulationHeLa CellsHuman Embryonic Stem CellsHumansLong Interspersed Nucleotide ElementsMesodermMicroRNAsPhenotypeRNARNA, Long NoncodingRNA, MessengerRNA, Small InterferingTranscription, GeneticTransgenesConceptsEmbryonic stem cellsESC differentiationTranscription networksSurveillance pathwayHuman embryonic stem cell differentiationGerm layersEmbryonic stem cell differentiationHuman embryonic stem cellsHuman ESC differentiationLINE-1 retrotransposonsStem cell differentiationTranscription factor crucialDevelopmental regulatorsMesendoderm formationDevelopmental genesRNA decayTranscription factorsSpecific miRNAsCell differentiationFactor crucialStem cellsPluripotencyExosomesDifferentiationRNA
2016
Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
Yang J, Tanaka Y, Seay M, Li Z, Jin J, Garmire LX, Zhu X, Taylor A, Li W, Euskirchen G, Halene S, Kluger Y, Snyder MP, Park IH, Pan X, Weissman SM. Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors. Nucleic Acids Research 2016, 45: 1281-1296. PMID: 28003475, PMCID: PMC5388401, DOI: 10.1093/nar/gkw1214.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsPrecursor cellsInduction of anemiaInterferon response genesG2/M phaseEarly precursor cellsHomeostatic cellsStages of differentiationTranscription factorsSurface markersCell cycle progressionLong-term hematopoietic stem cellsSpecific augmentationAnemic miceMarked increaseEarly hematopoietic precursorsHematopoietic precursorsStem cellsCycle progressionM phaseSingle-cell transcriptomicsCellsCell differentiationHematopoietic stressLineage-specific transcription factors
2015
Ethanol Upregulates NMDA Receptor Subunit Gene Expression in Human Embryonic Stem Cell-Derived Cortical Neurons
Xiang Y, Kim KY, Gelernter J, Park IH, Zhang H. Ethanol Upregulates NMDA Receptor Subunit Gene Expression in Human Embryonic Stem Cell-Derived Cortical Neurons. PLOS ONE 2015, 10: e0134907. PMID: 26266540, PMCID: PMC4534442, DOI: 10.1371/journal.pone.0134907.Peer-Reviewed Original ResearchConceptsCortical neuronsReceptor subunit gene expressionNeuron-specific biomarkerReverse transcription-quantitative polymerase chain reactionNMDA receptor subunit gene expressionChronic alcohol consumptionHuman brain cellsAlcohol-responsive genesNMDA receptor genesCalcium channel activityLive human brainQuantitative polymerase chain reactionSubunit gene expressionWithdrawal treatmentPolymerase chain reactionExpression changesEthanol exposureAlcohol abuseMultiple comparison correctionBrain cellsGene expression alterationsAlcohol consumptionNeuronal functionAlcohol metabolismNeuronsTranscriptome Signature and Regulation in Human Somatic Cell Reprogramming
Tanaka Y, Hysolli E, Su J, Xiang Y, Kim KY, Zhong M, Li Y, Heydari K, Euskirchen G, Snyder MP, Pan X, Weissman SM, Park IH. Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming. Stem Cell Reports 2015, 4: 1125-1139. PMID: 26004630, PMCID: PMC4471828, DOI: 10.1016/j.stemcr.2015.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceCellular ReprogrammingCyclin EEmbryonic Stem CellsGene Expression RegulationHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMolecular Sequence DataOctamer Transcription Factor-3Oncogene ProteinsPolymorphism, Single NucleotidePrincipal Component AnalysisProto-Oncogene Proteins c-mycRNASequence Analysis, RNASOXB1 Transcription FactorsTranscriptomeConceptsHuman somatic cell reprogrammingMonoallelic gene expressionSomatic cell reprogrammingPrevious transcriptome studiesHuman iPSC reprogrammingPluripotent stem cellsCell reprogrammingIPSC reprogrammingTranscriptome dataEarly reprogrammingTranscriptome studiesTranscriptome changesBiallelic expressionRNA-seqSomatic cellsExpression analysisGene expressionSpliced formsReprogrammingTranscriptome signaturesStem cellsInvaluable resourceCellular surface markersBiomedical researchCells
2013
Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2)
Tanaka Y, Kim KY, Zhong M, Pan X, Weissman SM, Park IH. Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2). Human Molecular Genetics 2013, 23: 1045-1055. PMID: 24129406, PMCID: PMC3900111, DOI: 10.1093/hmg/ddt500.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsMutant MECP2X chromosomeMethyl-CpGStem cellsGene expressionLong-range chromatin interactionsFundamental cellular physiologyRett syndromeMitochondrial membrane proteinInactive X chromosomeProtein 2Chromatin interactionsTranscriptional regulationTranscription regulatorsCellular physiologyTranscriptome analysisLoss of functionMembrane proteinsMeCP2 resultsDe novo mutationsRegulatory mechanismsMeCP2ChromosomesRTT patientsMeCP2 Regulates the Synaptic Expression of a Dysbindin-BLOC-1 Network Component in Mouse Brain and Human Induced Pluripotent Stem Cell-Derived Neurons
Larimore J, Ryder PV, Kim KY, Ambrose LA, Chapleau C, Calfa G, Gross C, Bassell GJ, Pozzo-Miller L, Smith Y, Talbot K, Park IH, Faundez V. MeCP2 Regulates the Synaptic Expression of a Dysbindin-BLOC-1 Network Component in Mouse Brain and Human Induced Pluripotent Stem Cell-Derived Neurons. PLOS ONE 2013, 8: e65069. PMID: 23750231, PMCID: PMC3672180, DOI: 10.1371/journal.pone.0065069.Peer-Reviewed Original ResearchConceptsMutant miceRett syndrome patientsBDNF contentDeficient miceSyndrome patientsInduced pluripotent stem cell-derived neuronsHuman Induced Pluripotent Stem Cell-Derived NeuronsPluripotent stem cell-derived neuronsStem cell-derived neuronsAutism spectrum disorderNormal human hippocampusCell-derived neuronsHuman inducible pluripotent stem cellsAsymmetric synapsesQuantitative real-time PCRHippocampal samplesReal-time PCRMouse hippocampusHuman neuronsPathogenic mechanismsQuantitative qRT-PCRQuantitative immunohistochemistryExpression of componentsSynaptic expressionInducible pluripotent stem cellsNotch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells
Lee JB, Werbowetski-Ogilvie TE, Lee JH, McIntyre BA, Schnerch A, Hong SH, Park IH, Daley GQ, Bernstein ID, Bhatia M. Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells. Blood 2013, 122: 1162-1173. PMID: 23733337, DOI: 10.1182/blood-2012-12-471649.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBasic Helix-Loop-Helix Transcription FactorsBiomarkersBlotting, WesternCell DifferentiationCell MovementCell ProliferationCells, CulturedDermisEmbryonic Stem CellsEndothelium, VascularFibroblastsFlow CytometryGene Expression ProfilingGene Expression RegulationHematopoiesisHematopoietic Stem CellsHomeodomain ProteinsHumansImmunoenzyme TechniquesInduced Pluripotent Stem CellsOligonucleotide Array Sequence AnalysisReceptor, Notch1Receptors, NotchRNA, Small InterferingSignal TransductionTranscription Factor HES-1ConceptsCell fate decisionsFate decisionsPluripotent stem cellsHematopoietic lineage specificationEarly human hematopoiesisFunction of NotchStem cellsHuman pluripotent stem cellsInduced pluripotent stem cellsRole of NotchEarly human developmentCommitted hematopoietic progenitorsFate specificationLineage specificationCellular processesNotch receptorsNotch signalingHematopoietic lineagesNotch pathwayBipotent precursorsNotch ligandsHuman hematopoiesisHuman embryonicUnappreciated roleToggle switch
2011
Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome
Kim KY, Hysolli E, Park IH. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 14169-14174. PMID: 21807996, PMCID: PMC3161557, DOI: 10.1073/pnas.1018979108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceBase SequenceBiomarkersCell DifferentiationChildChild, PreschoolChromosomes, Human, XEmbryonic Stem CellsFemaleFibroblastsGene Expression RegulationHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Methyl-CpG-Binding Protein 2Molecular Sequence DataNeuronsRett SyndromeX Chromosome InactivationConceptsX chromosomePluripotent stem cellsSingle active X chromosomeRett syndromeActive X chromosomePathophysiology of RTTX-chromosome inactivationStem cellsInduced pluripotent stem cellsRTT fibroblastsMurine genetic modelsMolecular dissectionChromosome inactivationFactors OCT4Methyl-CpGRTT phenotypeNeuronal differentiationChromosomesPurposeful hand movementsNormal developmentRTT modelModel of RTTProtein 2Maturation defectsNeuronal maturation
2010
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells
Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley GQ, Rinn JL. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature Genetics 2010, 42: 1113-1117. PMID: 21057500, PMCID: PMC3040650, DOI: 10.1038/ng.710.Peer-Reviewed Original ResearchMeSH KeywordsCellular ReprogrammingCluster AnalysisEmbryonic Stem CellsFibroblastsGene Expression RegulationGene Knockdown TechniquesGenetic LociHumansInduced Pluripotent Stem CellsOpen Reading FramesReverse Transcriptase Polymerase Chain ReactionRNA, UntranslatedTranscription FactorsTranscription, GeneticDirected differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
Grigoriadis AE, Kennedy M, Bozec A, Brunton F, Stenbeck G, Park IH, Wagner EF, Keller GM. Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells. Blood 2010, 115: 2769-2776. PMID: 20065292, PMCID: PMC2854424, DOI: 10.1182/blood-2009-07-234690.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsInduced pluripotent stem cellsStem cellsPrimitive streak-like populationHuman pluripotent stem cellsHuman cell typesEmbryonic bone developmentEmbryoid bodiesBone-resorbing osteoclastsMacrophage colony-stimulating factorIPS cellsHematopoietic cytokinesCell typesMolecular analysisCathepsin KHuman ESHematopoietic precursorsPrecursor populationAlphavbeta3 integrinBone developmentConfocal microscopyAbsence of RANKLNuclear factor-kappaB ligandDisease mechanismsSerum-free medium
2009
A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells
Lee JH, Park IH, Gao Y, Li JB, Li Z, Daley GQ, Zhang K, Church GM. A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells. PLOS Genetics 2009, 5: e1000718. PMID: 19911041, PMCID: PMC2766639, DOI: 10.1371/journal.pgen.1000718.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell DifferentiationCell LineCells, CulturedCluster AnalysisComputational BiologyDNA, ComplementaryFlow CytometryGene Expression RegulationHuman Genome ProjectHumansInduced Pluripotent Stem CellsNucleic Acid Amplification TechniquesOrgan SpecificityRegulatory Elements, TranscriptionalReproducibility of ResultsConceptsCis-regulatory variantsPluripotent stem cellsRegulatory polymorphismsGene expressionAllele-specific gene expressionIPS cellsPrimary fibroblastsCell typesAllele-specific expressionHigh-throughput sequencingStem cellsHuman iPS cellsSkin primary fibroblastsRegulatory variantsTissue-specific variantsX chromosomeDifferentiated derivativesExpression locusCell differentiationSpecific tissuesLymphoblastoid cellsDigital-RNAPadlock probesExpressionCells