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
2013
Therapeutic 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 models
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 mechanismsProtein
2011
Cell cycle adaptations of embryonic stem cells
Ballabeni A, Park IH, Zhao R, Wang W, Lerou PH, Daley GQ, Kirschner MW. Cell cycle adaptations of embryonic stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 19252-19257. PMID: 22084091, PMCID: PMC3228440, DOI: 10.1073/pnas.1116794108.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnaphase-Promoting Complex-CyclosomeAnimalsCell CycleCell Cycle ProteinsCell DifferentiationCell LineChromatinCyclin-Dependent Kinase 2Embryonic Stem CellsFlow CytometryImmunoblottingImmunoprecipitationMiceReal-Time Polymerase Chain ReactionUbiquitinationUbiquitin-Protein Ligase ComplexesConceptsHigh CDK activityCDK activityES cellsAPC/C activityUbiquitin ligase APC/CCell cycle adaptationsAPC/CEmbryonic stem cellsRapid cell cyclesMouse ES cellsMCM proteinsMitotic exitFactor Cdt1Emi1 proteinDNA replicationSomatic cellsCell cycleKey adaptationGap phaseS phaseC enzymesLevels of cyclinG1 phaseNormal progressionStem cellsStage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells
Nostro MC, Sarangi F, Ogawa S, Holtzinger A, Corneo B, Li X, Micallef SJ, Park IH, Basford C, Wheeler MB, Daley GQ, Elefanty AG, Stanley EG, Keller G. Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development 2011, 138: 861-871. PMID: 21270052, PMCID: PMC3035090, DOI: 10.1242/dev.055236.Peer-Reviewed Original ResearchConceptsHuman pluripotent stem cellsPluripotent stem cellsTGFβ family membersStem cellsPancreatic lineage cellsEndoderm fateEndoderm populationEndoderm inductionPancreatic specificationInsulin-expressing cellsBMP inhibitionPancreatic lineagePancreatic fateA SignalingInsulin-producing β-cellsGerm layersCanonical WntDevelopmental stagesActivin A signalingFamily membersLineage cellsWntInsulin expressionCell linesSpecific stages
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 differencesHESCsHuman Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms
Ni Z, Knorr DA, Clouser CL, Hexum MK, Southern P, Mansky LM, Park IH, Kaufman DS. Human Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms. Journal Of Virology 2010, 85: 43-50. PMID: 20962093, PMCID: PMC3014194, DOI: 10.1128/jvi.01774-10.Peer-Reviewed Original ResearchConceptsNK cellsHIV/AIDSAnti-HIV-1 immunityHIV-1-infected individualsAntibody-dependent cellular cytotoxicityTumor cellsCEM-GFP cellsFunctional NK cellsAnti-HIV-1 activityNatural killer cellsHIV-1 infectionProduction of chemokinesCellular mechanismsHIV-1 replicationStem cellsCellular immunotherapeutic approachesInnate immune systemVirus-infected cellsInfected targetsPluripotent stem cellsImmunotherapeutic approachesNatural killerKiller cellsCell-based therapiesT cellsRobust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity
Kim DS, Lee JS, Leem JW, Huh YJ, Kim JY, Kim HS, Park IH, Daley GQ, Hwang DY, Kim DW. Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity. Stem Cell Reviews And Reports 2010, 6: 270-281. PMID: 20376579, DOI: 10.1007/s12015-010-9138-1.Peer-Reviewed Original ResearchConceptsDifferentiation propensityStem cell linesCell lineagesNeural differentiationHuman embryonic stem cell linesEmbryonic stem cell linesCell typesActivin/NodalHuman pluripotent stem cell linesDesirable cell typesSpecific cell typesCell linesModulation of intracellularPluripotent stem cellsPluripotent stem cell lineBMP pathwaySpecific lineagesIPS cellsUndifferentiated cellsLineagesDifferentiation potentialHuman ESStem cellsNeural cellsDifferentiationTelomere 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
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 probesExpressionCellsLive cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells
Chan EM, Ratanasirintrawoot S, Park IH, Manos PD, Loh YH, Huo H, Miller JD, Hartung O, Rho J, Ince TA, Daley GQ, Schlaeger TM. Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nature Biotechnology 2009, 27: 1033-1037. PMID: 19826408, DOI: 10.1038/nbt.1580.Peer-Reviewed Original ResearchCardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells
Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, Gepstein L. Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells. Circulation 2009, 120: 1513-1523. PMID: 19786631, DOI: 10.1161/circulationaha.109.868885.Peer-Reviewed Original ResearchConceptsTranscription factorsHiPS cellsCardiomyocyte differentiationCardiac-specific transcription factorsInduced pluripotent stem cellsGene expression studiesHuman induced pluripotent stem cellsStem cell linesPluripotent stem cellsCardiomyocyte differentiation potentialPluripotent stem cell lineStructural geneContracting embryoid bodiesCardiomyocyte differentiation processTranslational cardiovascular researchEmbryoid bodiesExpression studiesDifferentiation systemDifferentiation processCardiovascular regenerative medicineSarcomeric proteinsDifferentiation potentialIon channelsAdult fibroblastsFunctional propertiesA role for Lin28 in primordial germ-cell development and germ-cell malignancy
West JA, Viswanathan SR, Yabuuchi A, Cunniff K, Takeuchi A, Park IH, Sero JE, Zhu H, Perez-Atayde A, Frazier AL, Surani MA, Daley GQ. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature 2009, 460: 909-913. PMID: 19578360, PMCID: PMC2729657, DOI: 10.1038/nature08210.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineChromosomal Proteins, Non-HistoneEmbryonic Stem CellsFemaleGene Expression Regulation, NeoplasticGerm CellsHumansMiceMice, Inbred C57BLNeoplasms, Germ Cell and EmbryonalPositive Regulatory Domain I-Binding Factor 1Repressor ProteinsRNA-Binding ProteinsTranscription FactorsTransgenesGene Targeting of a Disease-Related Gene in Human Induced Pluripotent Stem and Embryonic Stem Cells
Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK, Chen G, Ye Z, Park IH, Daley GQ, Porteus MH, Joung JK, Cheng L. Gene Targeting of a Disease-Related Gene in Human Induced Pluripotent Stem and Embryonic Stem Cells. Cell Stem Cell 2009, 5: 97-110. PMID: 19540188, PMCID: PMC2720132, DOI: 10.1016/j.stem.2009.05.023.Peer-Reviewed Original ResearchConceptsHuman ES cellsZinc finger nucleasesSequence-specific double-strand breaksEngineered zinc finger nucleasesGene targetingGFP reporter geneEmbryonic stem cellsDouble-strand breaksHuman Induced Pluripotent StemSpecific genetic modificationsHuman iPS cellsES cellsFinger nucleasesTransgene expressionInduced pluripotent stemHomologous recombinationGFP geneInsertional mutagenesisReporter geneDifferent genesGenetic modificationIPS cellsDonor DNAGenesCell types
2008
Regulatory networks define phenotypic classes of human stem cell lines
Müller FJ, Laurent LC, Kostka D, Ulitsky I, Williams R, Lu C, Park IH, Rao MS, Shamir R, Schwartz PH, Schmidt NO, Loring JF. Regulatory networks define phenotypic classes of human stem cell lines. Nature 2008, 455: 401-405. PMID: 18724358, PMCID: PMC2637443, DOI: 10.1038/nature07213.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAnimalsArtificial IntelligenceCell DifferentiationCell LineComputational BiologyDatabases, FactualEmbryonic Stem CellsGene Expression ProfilingHumansMiceMultipotent Stem CellsOligonucleotide Array Sequence AnalysisOocytesPhenotypePluripotent Stem CellsProtein BindingStem CellsConceptsStem cell linesStem cellsCell linesCell typesProtein-protein networkHuman stem cell linesDifferent human cell linesSpecific molecular networksPluripotent stem cell lineHuman stem cellsHuman cell linesRegulatory networksTranscriptional profilesBioinformatics analysisPhenotypic classesMolecular networksNeural stem cell lineLimited repertoireTight controlCellsCell samplesPluripotencyEmbryosLinesBroad rangeDisease-Specific Induced Pluripotent Stem Cells
Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-Specific Induced Pluripotent Stem Cells. Cell 2008, 134: 877-886. PMID: 18691744, PMCID: PMC2633781, DOI: 10.1016/j.cell.2008.07.041.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDown syndromeBecker muscular dystrophyType 1 diabetes mellitusHuntington's diseaseStem cellsPluripotent stem cellsDiabetes mellitusDisease-SpecificLesch-Nyhan syndromeDisease-specific stem cellsDiseased patientsCarrier stateTumor cell linesDiseaseSyndromeMuscular dystrophyAdenosine deaminasePatientsDrug developmentInduced pluripotent stem cellsType IIICell linesDiamond syndromeDisease investigation