2021
Regional specification and complementation with non-neuroectodermal cells in human brain organoids
Tanaka Y, Park IH. Regional specification and complementation with non-neuroectodermal cells in human brain organoids. Journal Of Molecular Medicine 2021, 99: 489-500. PMID: 33651139, PMCID: PMC8026433, DOI: 10.1007/s00109-021-02051-9.Peer-Reviewed Original ResearchAnimalsBrainCellular Reprogramming TechniquesEmbryoid BodiesEndothelial CellsFetusFibroblast Growth Factor 2Hedgehog ProteinsHuman Umbilical Vein Endothelial CellsHumansInduced Pluripotent Stem CellsIntercellular Signaling Peptides and ProteinsMicrogliaNeuronsOrgan SpecificityOrganogenesisOrganoidsRetinaSpinal CordWnt Signaling Pathway
2020
Deconstructing and reconstructing the human brain with regionally specified brain organoids
Xiang Y, Cakir B, Park IH. Deconstructing and reconstructing the human brain with regionally specified brain organoids. Seminars In Cell And Developmental Biology 2020, 111: 40-51. PMID: 32553582, DOI: 10.1016/j.semcdb.2020.05.023.Peer-Reviewed Original ResearchDysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons
Xiang Y, Tanaka Y, Patterson B, Hwang SM, Hysolli E, Cakir B, Kim KY, Wang W, Kang YJ, Clement EM, Zhong M, Lee SH, Cho YS, Patra P, Sullivan GJ, Weissman SM, Park IH. Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons. Molecular Cell 2020, 79: 84-98.e9. PMID: 32526163, PMCID: PMC7375197, DOI: 10.1016/j.molcel.2020.05.016.Peer-Reviewed Original ResearchConceptsMECP2 mutant neuronsEnhancer-promoter interactionsRett syndromeRTT-like phenotypesChromatin bindingMeCP2 functionMethyl-CpGAbnormal transcriptionRTT etiologyMutant neuronsBET inhibitorsPotential therapeutic opportunitiesMECP2 mutationsProtein 2Human brain organoidsFunctional phenotypeJQ1BRD4Therapeutic opportunitiesBrain organoidsFunction underliesMutationsPhenotypeHuman brain culturesCritical driver
2017
Bisulfite-independent analysis of CpG island methylation enables genome-scale stratification of single cells
Han L, Wu HJ, Zhu H, Kim KY, Marjani SL, Riester M, Euskirchen G, Zi X, Yang J, Han J, Snyder M, Park IH, Irizarry R, Weissman SM, Michor F, Fan R, Pan X. Bisulfite-independent analysis of CpG island methylation enables genome-scale stratification of single cells. Nucleic Acids Research 2017, 45: e77-e77. PMID: 28126923, PMCID: PMC5605247, DOI: 10.1093/nar/gkx026.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCell Line, TumorChromosome MappingCpG IslandsDNA MethylationDNA Restriction EnzymesEpigenesis, GeneticFibroblastsGenetic VariationGenome, HumanHigh-Throughput Nucleotide SequencingHumansInduced Pluripotent Stem CellsK562 CellsLymphocytesPromoter Regions, GeneticSingle-Cell AnalysisConceptsSingle cellsMethylation-sensitive restriction enzyme digestionCpG methylation patternsDNA bisulfite sequencingInduced pluripotent stem cellsSingle-cell levelCpG island methylationPluripotent stem cellsHeterogeneous cell populationsMultiple displacement amplificationEpigenetic heterogeneityMethylation sequencingBisulfite sequencingENCODE dataMethylation patternsMethylation differencesMethylation profilesRestriction enzyme digestionIsland methylationIndividual cellsHematopoietic cellsStem cellsSmall populationSequencingEnzyme digestion
2016
Modeling and correction of structural variations in patient-derived iPSCs using CRISPR/Cas9
Park CY, Sung JJ, Choi SH, Lee DR, Park IH, Kim DW. Modeling and correction of structural variations in patient-derived iPSCs using CRISPR/Cas9. Nature Protocols 2016, 11: 2154-2169. PMID: 27711053, DOI: 10.1038/nprot.2016.129.Peer-Reviewed Original ResearchRegulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family
Hysolli E, Tanaka Y, Su J, Kim KY, Zhong T, Janknecht R, Zhou XL, Geng L, Qiu C, Pan X, Jung YW, Cheng J, Lu J, Zhong M, Weissman SM, Park IH. Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. Stem Cell Reports 2016, 7: 43-54. PMID: 27373925, PMCID: PMC4945581, DOI: 10.1016/j.stemcr.2016.05.014.Peer-Reviewed Original ResearchMeSH KeywordsCellular ReprogrammingDNA MethylationEpigenesis, GeneticHuman Embryonic Stem CellsHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4MicroRNAsConceptsDNA methylation stateEmbryonic stem cellsInduced pluripotent stem cellsHuman somatic cell reprogrammingSomatic cell reprogrammingMethylation stateCell reprogrammingMiR-29 familyDNA methylation landscapeImportant epigenetic regulatorsStem cellsOverexpression of Oct4Global DNA methylationMiRNA-based approachesPluripotent stem cellsMethylation landscapeHistone modificationsDNA demethylationEpigenomic changesEarly reprogrammingEpigenetic regulatorsEpigenetic differencesDNA methylationHydroxymethylation analysisReprogramming
2015
Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice
Abed S, Tubsuwan A, Chaichompoo P, Park IH, Pailleret A, Benyoucef A, Tosca L, De Dreuzy E, Paulard A, Granger-Locatelli M, Relouzat F, Prost S, Tachdjian G, Fucharoen S, Daley GQ, Payen E, Chrétien S, Leboulch P, Maouche-Chrétien L. Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice. Haematologica 2015, 100: e428-e431. PMID: 26088930, PMCID: PMC4591782, DOI: 10.3324/haematol.2015.127373.Peer-Reviewed Original ResearchAnimalsHematopoietic Stem Cell TransplantationHematopoietic Stem CellsImmunocompromised HostInduced Pluripotent Stem CellsMacacaMiceModels, AnimalTranscriptome 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 researchCellsRole of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC
Kwon YW, Paek JS, Cho HJ, Lee CS, Lee HJ, Park IH, Roh TY, Kang CM, Yang HM, Park YB, Kim HS. Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC. Biomaterials 2015, 59: 102-115. PMID: 25956855, DOI: 10.1016/j.biomaterials.2015.03.031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationEmbryonic Stem CellsInduced Pluripotent Stem CellsMiceMice, Inbred C57BLTranscription FactorsConceptsMES cellsSomatic cellsCell extractsProtein extractsGlobal gene expressionES-like cellsMouse iPS cellsPluripotent stem cellsCell-derived proteinsHistone modificationsFull reprogrammingEpigenetic statusDNA methylationZscan4Developmental potencyIPSC derivationGene expressionGenomic DNAIPS cellsAdult fibroblastsKey moleculesStem cellsProteinCellsColonies
2014
X Chromosome of Female Cells Shows Dynamic Changes in Status during Human Somatic Cell Reprogramming
Kim KY, Hysolli E, Tanaka Y, Wang B, Jung YW, Pan X, Weissman SM, Park IH. X Chromosome of Female Cells Shows Dynamic Changes in Status during Human Somatic Cell Reprogramming. Stem Cell Reports 2014, 2: 896-909. PMID: 24936474, PMCID: PMC4050354, DOI: 10.1016/j.stemcr.2014.04.003.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCellular ReprogrammingChromosomes, Human, XFemaleHumansInduced Pluripotent Stem CellsPolymorphism, Single NucleotideConceptsX chromosome stateInactive X chromosomeActive X chromosomeX chromosomeChromosome stateHuman somatic cell reprogrammingIPSC clonesSomatic cell reprogrammingX chromosome reactivationStem cellsEmbryonic stem cellsPluripotent stem cellsHuman iPSC clonesEpigenetic stateCell reprogrammingFemale iPSCsFemale cellsChromosomesHuman iPSCsParental cellsDisease modelingDynamic changesRobust reactivationIPSCsClones
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 ResearchMeSH KeywordsCells, CulturedEmbryonic Stem CellsFemaleGene Expression RegulationGene OntologyHumansInduced Pluripotent Stem CellsMethyl-CpG-Binding Protein 2MutationRett SyndromeTranscription, GeneticTranscriptomeConceptsPluripotent 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 patientsInvestigation of Rett syndrome using pluripotent stem cells
Dajani R, Koo S, Sullivan GJ, Park I. Investigation of Rett syndrome using pluripotent stem cells. Journal Of Cellular Biochemistry 2013, 114: 2446-2453. PMID: 23744605, PMCID: PMC3773984, DOI: 10.1002/jcb.24597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationHumansInduced Pluripotent Stem CellsMethyl-CpG-Binding Protein 2Rett SyndromeConceptsPluripotent stem cellsStem cellsRett syndromeFunction of MeCP2Pathophysiology of RTTEmbryonic stem cellsEpigenetic instabilityTranscription factorsDe novo mutationsRTT phenotypeCurrent iPSCHuman diseasesMeCP2Novo mutationsIPSCsCellsNeurodevelopmental disordersOverexpressionMutationsPhenotypeMurine modelRecapitulationMaintenanceIdentificationTherapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
Chang DJ, Lee N, Park IH, Choi C, Jeon I, Kwon J, Oh SH, Shin DA, Tae J, Lee DR, Lee H, Hong K, Daley G, Song J, Moon H. Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke. Cell Transplantation 2013, 22: 1427-1440. PMID: 23044029, DOI: 10.3727/096368912x657314.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBehavior, AnimalCell DifferentiationCell LineCell TrackingDisease Models, AnimalGliosisHumansInduced Pluripotent Stem CellsInfarction, Middle Cerebral ArteryInflammationMagnetic Resonance ImagingMaleMiceNeural Stem CellsNeurogenesisNeuronsRatsRats, Sprague-DawleyStem Cell TransplantationStrokeConceptsMiddle cerebral artery occlusionNeural precursor cellsNeural stem cellsStroke-induced inflammatory responseTherapeutic potentialMCAO stroke modelCerebral artery occlusionPeri-infarct areaTreatment of strokeLimited therapeutic optionsStem cellsAutologous cell therapyEndogenous neurogenesisExperimental strokePluripotent stem cellsArtery occlusionIschemic strokeBehavioral recoveryTherapeutic optionsNeurological functionInflammatory responseRobust therapeutic potentialStroke modelMRI resultsAnimal modelsComment on “Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells”
Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. Comment on “Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells”. Science Translational Medicine 2013, 5: 188le2. PMID: 23740897, PMCID: PMC3936961, DOI: 10.1126/scitranslmed.3005065.Peer-Reviewed Original ResearchAmyotrophic Lateral SclerosisDrug Evaluation, PreclinicalHumansInduced Pluripotent Stem CellsMotor NeuronsMeCP2 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 switchPluripotent Stem Cell Models of Shwachman-Diamond Syndrome Reveal a Common Mechanism for Pancreatic and Hematopoietic Dysfunction
Tulpule A, Kelley JM, Lensch MW, McPherson J, Park IH, Hartung O, Nakamura T, Schlaeger TM, Shimamura A, Daley GQ. Pluripotent Stem Cell Models of Shwachman-Diamond Syndrome Reveal a Common Mechanism for Pancreatic and Hematopoietic Dysfunction. Cell Stem Cell 2013, 12: 727-736. PMID: 23602541, PMCID: PMC3755012, DOI: 10.1016/j.stem.2013.04.002.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsPluripotent stem cell modelsStem cell modelShwachman-Diamond syndromeHuman pluripotent stem cell modelSBDS protein expressionEmbryonic stem cellsDiamond syndrome (SBDS) geneStem cell linesHematopoietic dysfunctionPluripotent stem cell lineHematopoietic phenotypeInduced pluripotent stem cell lineHematopoietic differentiationCell modelTransgene rescueShwachman-BodianSyndrome geneHuman diseasesElevated protease levelsNovel insightsMechanistic linkStem cellsEnhanced apoptosisProtein expressionTransformation of somatic cells into stem cell‐like cells under a stromal niche
Lee ST, Gong SP, Yum KE, Lee EJ, Lee CH, Choi JH, Kim DY, Han H, Kim K, Hysolli E, Ahn JY, Park I, Han JY, Jeong J, Lim JM. Transformation of somatic cells into stem cell‐like cells under a stromal niche. The FASEB Journal 2013, 27: 2644-2656. PMID: 23580613, PMCID: PMC4050423, DOI: 10.1096/fj.12-223065.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AggregationCell DedifferentiationCell FusionCells, CulturedChromosome AberrationsCoculture TechniquesEmbryo, MammalianEmbryonic Stem CellsFemaleFibroblastsGene Expression ProfilingInduced Pluripotent Stem CellsKaryotypingMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBAMice, Inbred ICRMicroscopy, Electron, TransmissionOligonucleotide Array Sequence AnalysisOvarySpecies SpecificityStem Cell NicheStem CellsConceptsEmbryonic stem cellsColony-forming fibroblastsParthenogenetic embryonic stem cellsSomatic cellsGenomic single nucleotide polymorphismsAcquisition of pluripotencySomatic cell plasticityPluripotency gene expressionStem cellsInner cell massStem cell-like cellsCell cycle-related proteinsPluripotent stem cellsSomatic genomeCycle-related proteinsGenomic plasticityCell-like cellsSingle nucleotide polymorphismsCell plasticityESC coloniesGenetic manipulationHeterologous recombinationEmbryonic fibroblastsImprinting patternGene expression
2012
Impact of Retrotransposons in Pluripotent Stem Cells
Tanaka Y, Chung L, Park IH. Impact of Retrotransposons in Pluripotent Stem Cells. Molecules And Cells 2012, 34: 509-516. PMID: 23135636, PMCID: PMC3784326, DOI: 10.1007/s10059-012-0242-8.Peer-Reviewed Original ResearchMeSH KeywordsAlu ElementsCell DifferentiationEmbryonic Stem CellsGenome, HumanHumansInduced Pluripotent Stem CellsPluripotent Stem CellsRetroelementsDevelopment of a novel two-dimensional directed differentiation system for generation of cardiomyocytes from human pluripotent stem cells
Moon SH, Ban K, Kim C, Kim SS, Byun J, Song MK, Park IH, Yu SP, Yoon YS. Development of a novel two-dimensional directed differentiation system for generation of cardiomyocytes from human pluripotent stem cells. International Journal Of Cardiology 2012, 168: 41-52. PMID: 23044428, PMCID: PMC3556195, DOI: 10.1016/j.ijcard.2012.09.077.Peer-Reviewed Original Research