2017
Genetic and Epigenetic Considerations in iPSC Technology
Tanaka Y, Park I. Genetic and Epigenetic Considerations in iPSC Technology. 2017, 51-86. DOI: 10.1201/b21629-3.Peer-Reviewed Original ResearchInduced pluripotent stem cell reprogrammingMethylation patternsN-terminal tail domainsHigher-order structure of chromatinInduced pluripotent stem cellsSomatic cellsDNA methylation patternsStructure of chromatinDeoxyribonucleic acidEfficiency of iPSC generationPosttranslational modificationsEpigenetic modificationsHistone octamerDNA wrappingEpigenetic changesHigher-order structureSomatic reprogrammingEpigenetic modulationEpigenetic considerationsReprogrammingHistonePluripotent statePluripotent stem cellsIPSC generationOriginal somatic cellsBisulfite-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
Regulation 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 ResearchConceptsDNA 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
2013
Notch-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
2012
Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient
Chae JI, Kim DW, Lee N, Jeon YJ, Jeon I, Kwon J, Kim J, Soh Y, Lee DS, Seo KS, Choi NJ, Park BC, Kang SH, Ryu J, Oh SH, Shin DA, Lee DR, Tae J, Park IH, Daley GQ, Song J. Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient. Biochemical Journal 2012, 446: 359-371. PMID: 22694310, DOI: 10.1042/bj20111495.Peer-Reviewed Original ResearchConceptsHD-iPSCsProteomic analysisCellular disease-modelling systemsHD-iPSCComparative proteomic analysisQuantitative proteomic analysisStress-related proteinsDifferent biological processesP53-mediated apoptotic pathwayInduced pluripotent stem cellsOxidative stress-related proteinsExpression of cytoskeletonPluripotent stem cellsDisease model systemsOxidative stressPrx familyProteomic profilesUndifferentiated stageBiological processesApoptotic pathwayNeuronal differentiationCell deathNeurodegenerative genetic disorderNeurodegeneration mechanismsProteinCellular reprogramming: a novel tool for investigating autism spectrum disorders
Kim KY, Jung YW, Sullivan GJ, Chung L, Park IH. Cellular reprogramming: a novel tool for investigating autism spectrum disorders. Trends In Molecular Medicine 2012, 18: 463-471. PMID: 22771169, PMCID: PMC3785941, DOI: 10.1016/j.molmed.2012.06.002.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsNovel ASD genesUse of iPSCsHuman disease modelsPluripotent stem cellsSomatic cellsGenomic technologiesAdvanced geneticsASD genesCellular modelStem cellsScreening platformSmall moleculesDisease modelsNovel toolNeurodevelopmental disordersUnprecedented opportunityCellsGenesGeneticsCell therapyAutism spectrum disorderMurine modelFuture perspectivesReciprocal social interactionExcision of a Viral Reprogramming Cassette by Delivery of Synthetic Cre mRNA
Loh Y, Yang JC, De Los Angeles A, Guo C, Cherry A, Rossi DJ, Park I, Daley GQ. Excision of a Viral Reprogramming Cassette by Delivery of Synthetic Cre mRNA. Current Protocols In Stem Cell Biology 2012, 21: 4a.5.1-4a.5.16. PMID: 22605648, PMCID: PMC3397830, DOI: 10.1002/9780470151808.sc04a05s21.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsTransgene-free methodsHuman iPS cellsResidual transgene expressionPatient-specific induced pluripotent stem cellsIPS cellsInduced pluripotent stem cellsStem cellsTransgene expressionFree humanHuman OCT4MRNA transfectionDrug screeningProtein transductionCre mRNADifferentiation potentialCell therapySingle vectorLow efficiencyCassetteRetroviral transfectionCre recombinaseEfficiencyTransfectionExperimental generationReprogramming human somatic cells into induced pluripotent stem cells (iPSCs) using retroviral vector with GFP.
Kim KY, Hysolli E, Park IH. Reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) using retroviral vector with GFP. Journal Of Visualized Experiments 2012 PMID: 22491226, PMCID: PMC3466658, DOI: 10.3791/3804.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsInduced pluripotent stem cellsHuman somatic cellsHuman induced pluripotent stem cellsPluripotent stem cellsSomatic cellsIPSC coloniesStem cellsESC culture conditionsEmbryonic stem cellsPluripotency genesTranscription factorsRetroviral transgenesEctopic expressionGFP fluorescenceRetroviral vectorsHuman fibroblast cellsFibroblast cellsGFPCulture conditionsCellsAutologous cellsCellular sourceColoniesSurface markers
2011
Gene-Correction Rescues Reprogramming of Fanconi Anemia Fibroblasts and Enables Hematopoietic Differentiation of FA Induced Pluripotent Stem Cells in Vitro and In Vivo
Mueller L, Milsom M, Harris C, Vyas R, Brumme K, Parmar K, Schambach A, Grassman E, Park I, Wendy L, Strait K, Schlaeger T, Devine A, D'Andrea A, Daley G, Williams D. Gene-Correction Rescues Reprogramming of Fanconi Anemia Fibroblasts and Enables Hematopoietic Differentiation of FA Induced Pluripotent Stem Cells in Vitro and In Vivo. Blood 2011, 118: 672. DOI: 10.1182/blood.v118.21.672.672.Peer-Reviewed Original ResearchFA cellsFA pathwayFanconi anemiaPluripotent stem cellsHematopoietic differentiationGenomic instabilityStem cellsIPSC linesDouble-strand DNA breaksHematopoietic cellsFANCD2 foci formationPatient iPSC linesHematopoietic differentiation potentialFanconi anemia fibroblastsTail-tip fibroblastsInduced pluripotent stem cellsDefective DNA repairGreen fluorescent proteinFatal bone marrow failureGenomic integritySignificant chromosomal imbalancesHematopoietic stem cellsComparative genomic hybridizationComplementation groupsDNA repairNeuronal 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 maturationAnalysis of Differential Proteomes of Induced Pluripotent Stem Cells by Protein-Based Reprogramming of Fibroblasts
Jin J, Kwon YW, Paek JS, Cho HJ, Yu J, Lee JY, Chu IS, Park IH, Park YB, Kim HS, Kim Y. Analysis of Differential Proteomes of Induced Pluripotent Stem Cells by Protein-Based Reprogramming of Fibroblasts. Journal Of Proteome Research 2011, 10: 977-989. PMID: 21175196, DOI: 10.1021/pr100624f.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsES cell linesPluripotent stem cellsIPS cellsDifferential proteomeGlobal gene expression patternsCell extractsGlobal gene expression analysisCell linesReprogramming of fibroblastsSpecific transcription factorsProtein synthetic machineryPluripotent ES cellsGene expression patternsStem cellsViral transductionMES cell linesGene expression analysisTranscription factorsSynthetic machineryExpression analysisRetroviral integrationES cellsExpression patternsStem cell-based approaches
2010
Induced pluripotent stem cells: A novel frontier in the study of human primary immunodeficiencies
Pessach IM, Ordovas-Montanes J, Zhang SY, Casanova JL, Giliani S, Gennery AR, Al-Herz W, Manos PD, Schlaeger TM, Park IH, Rucci F, Agarwal S, Mostoslavsky G, Daley GQ, Notarangelo LD. Induced pluripotent stem cells: A novel frontier in the study of human primary immunodeficiencies. Journal Of Allergy And Clinical Immunology 2010, 127: 1400-1407.e4. PMID: 21185069, PMCID: PMC3081993, DOI: 10.1016/j.jaci.2010.11.008.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityCell DedifferentiationCell DifferentiationCell LineCell TransdifferentiationDNAGene ExpressionGenes, mycHumansImmunity, InnateImmunologic Deficiency SyndromesInduced Pluripotent Stem CellsKaryotypingKruppel-Like Factor 4Kruppel-Like Transcription FactorsOctamer Transcription Factor-3Proto-Oncogene MasSOXB1 Transcription FactorsConceptsInduced pluripotent stem cellsKrueppel-like factor 4Pluripotent stem cellsStem cellsIPSC linesHuman embryonic stem cellsEmbryonic stem cellsExpression of genesTranscription factor 4Patient-derived iPSC linesFactor 4Region Y-box 2Patient dermal fibroblastsTranscription factorsSomatic cellsDermal fibroblastsHuman primary immunodeficienciesEmbryoid bodiesExogenous expressionHuman diseasesGene correctionCell typesProto-oncogeneEmbryonic layersPolycistronic lentiviral vectorMicroRNA Profiling Reveals Two Distinct p53-Related Human Pluripotent Stem Cell States
Neveu P, Kye MJ, Qi S, Buchholz DE, Clegg DO, Sahin M, Park IH, Kim KS, Daley GQ, Kornblum HI, Shraiman BI, Kosik KS. MicroRNA Profiling Reveals Two Distinct p53-Related Human Pluripotent Stem Cell States. Cell Stem Cell 2010, 7: 671-681. PMID: 21112562, DOI: 10.1016/j.stem.2010.11.012.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsPluripotent stem cell stateEmbryonic stem cellsStem cell stateCell statesDifferentiated cellsStem cellsCell linesPluripotent stem cellsHuman cell linesGene setsMiRNA expression levelsMiR-92Cell line originMicroRNA profilingCancer cell linesLine originMiRNA profilesExpression levelsPluripotencyCancer cellsMiR-141CellsSubtle differencesHESCsLarge 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, GeneticHematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome)
Tolar J, Park IH, Xia L, Lees CJ, Peacock B, Webber B, McElmurry RT, Eide CR, Orchard PJ, Kyba M, Osborn MJ, Lund TC, Wagner JE, Daley GQ, Blazar BR. Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome). Blood 2010, 117: 839-847. PMID: 21037085, PMCID: PMC3035077, DOI: 10.1182/blood-2010-05-287607.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell DifferentiationCells, CulturedChild, PreschoolDNA MethylationHEK293 CellsHematopoietic SystemHomeodomain ProteinsHumansIduronidaseInduced Pluripotent Stem CellsInfantKeratinocytesKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMesodermMiceMucopolysaccharidosis INanog Homeobox ProteinOctamer Transcription Factor-3Promoter Regions, GeneticProto-Oncogene Proteins c-mycSOXB1 Transcription FactorsStromal CellsTransfectionConceptsHematopoietic cell transplantationMPS IHMucopolysaccharidosis type IL-iduronidaseNonhematopoietic cellsStem cellsLife-saving measureInduced pluripotent stem cellsAutologous stem cellsAutologous hematopoietic graftsType IPluripotent stem cellsAllogeneic transplantationSignificant morbidityImmunologic complicationsInsidious onsetCell transplantationHematopoietic graftsImmune reactionsAnatomical sitesCongenital deficiencyIdeal graftDonor cellsLysosomal storageKnown benefitsTelomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Agarwal S, Loh YH, McLoughlin EM, Huang J, Park IH, Miller JD, Huo H, Okuka M, dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 2010, 464: 292-296. PMID: 20164838, PMCID: PMC3058620, DOI: 10.1038/nature08792.Peer-Reviewed Original ResearchConceptsDyskeratosis congenita cellsDyskeratosis congenita patientsPluripotency-associated transcription factorsInduced pluripotent stem cellsPluripotent stem cellsTelomerase componentsTranscription factorsIPS cell technologyGenetic lesionsMultiple tissuesStem cellsDyskeratosis congenitaTERC expressionCellsElongationTelomeraseMaintenanceExpressionCell technologyDirected 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
Hematopoietic Development From Human Induced Pluripotent Stem Cells.
Grauer M, Konantz M, Niebuhr N, Kanz L, Park I, Daley G, Lengerke C. Hematopoietic Development From Human Induced Pluripotent Stem Cells. Blood 2009, 114: 2530. DOI: 10.1182/blood.v114.22.2530.2530.Peer-Reviewed Original ResearchMouse embryonic stem cellsEmbryonic stem cellsInduced pluripotent stem cellsPluripotent stem cellsHuman embryonic stem cellsHematopoietic stem cellsHuman induced pluripotent stem cellsHuman iPS cellsIPS cellsCdx genesHematopoietic developmentBlood lineagesStem cellsBlood formationEmbryonic blood formationGenetic modificationHuman developmental hematopoiesisDifferentiated somatic cellsHuman pluripotent stem cell linesStem cell linesIrradiated adult micePluripotent stem cell lineDevelopmental hematopoiesisHematopoietic genesHox genesTelomere Elongation in Dyskeratosis Congenita Induced Pluripotent Stem Cells.
Agarwal S, Loh Y, McLoughlin E, Huang J, Park I, Miller J, Huo H, Okuka M, dos Reis R, Loewer S, Keefe D, Goldman F, Klingelhutz A, Liu L, Daley G. Telomere Elongation in Dyskeratosis Congenita Induced Pluripotent Stem Cells. Blood 2009, 114: 497. DOI: 10.1182/blood.v114.22.497.497.Peer-Reviewed Original ResearchTelomerase RNA componentAutosomal dominant dyskeratosis congenitaPatient-specific iPS cellsInduced pluripotent stemIPS cellsDominant dyskeratosis congenitaSelf-renewal capacitySomatic cellsTERC locusDyskeratosis congenitaPluripotency-associated transcription factorsPrimary somatic cellsHallmarks of pluripotencyInduced pluripotent stem cellsTelomere lengthHuman iPS cellsHuman degenerative disordersPluripotent stem cellsTranscriptional silencingPluripotent stateTelomerase functionSteady-state levelsTranscription factorsRNA componentIPS linesDifferential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts
Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, Herb B, Ladd-Acosta C, Rho J, Loewer S, Miller J, Schlaeger T, Daley GQ, Feinberg AP. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nature Genetics 2009, 41: 1350-1353. PMID: 19881528, PMCID: PMC2958040, DOI: 10.1038/ng.471.Peer-Reviewed Original Research