2021
Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts
Cho J, Kim S, Lee H, Rah W, Cho HC, Kim NK, Bae S, Shin DH, Lee MG, Park IH, Tanaka Y, Shin E, Yi H, Han JW, Hwang PTJ, Jun HW, Park HJ, Cho K, Lee SW, Jung JK, Levit RD, Sussman MA, Harvey RP, Yoon YS. Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts. Nature Biomedical Engineering 2021, 5: 880-896. PMID: 34426676, PMCID: PMC8809198, DOI: 10.1038/s41551-021-00783-0.Peer-Reviewed Original ResearchConceptsDirect reprogrammingMouse tail-tip fibroblastsBone morphogenetic protein 4Smooth muscle cellsTail-tip fibroblastsMuscle cellsSomatic cellsEndothelial cellsReprogrammingCell typesTissue-like structuresMouse fibroblastsProtein 4Gap junctionsCardiovascular tissuesVessel formationDisease modellingDrug discoveryImmature characteristicsFibroblastsCellsMouse heartsCardiomyocytesTissueHost cardiomyocytes
2018
Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a
Kim KY, Tanaka Y, Su J, Cakir B, Xiang Y, Patterson B, Ding J, Jung YW, Kim JH, Hysolli E, Lee H, Dajani R, Kim J, Zhong M, Lee JH, Skalnik D, Lim JM, Sullivan GJ, Wang J, Park IH. Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nature Communications 2018, 9: 2583. PMID: 29968706, PMCID: PMC6030064, DOI: 10.1038/s41467-018-04818-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCAAT-Enhancer-Binding ProteinsCellular ReprogrammingCellular Reprogramming TechniquesChimeraDNA MethylationEpigenesis, GeneticFemaleFibroblastsGene Knockout TechniquesHEK293 CellsHistone CodeHistone-Lysine N-MethyltransferaseHistonesHumansMaleMesodermMiceMouse Embryonic Stem CellsNeural PlateNuclear ProteinsPrimary Cell CultureRecombinant ProteinsUbiquitin-Protein LigasesConceptsEmbryonic stem cellsUnique epigenetic statesBivalent histone modificationsRecruitment of DNMT1Bivalent histone marksCell typesDNA-binding proteinsSpecialized cell typesStem cellsPluripotent stem cellsTrithorax groupBivalent domainsMesoderm specificationCOMPASS complexHeterochromatin formationEpigenetic stateCell specificationHistone marksLineage specificationHistone modificationsEpigenetic regulationSpecific lineagesDNA methylationTranscriptional marksEpigenetic changes
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
Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2
Lee S, Park C, Han JW, Kim JY, Cho K, Kim EJ, Kim S, Lee SJ, Oh SY, Tanaka Y, Park IH, An HJ, Shin CM, Sharma S, Yoon YS. Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2. Circulation Research 2016, 120: 848-861. PMID: 28003219, PMCID: PMC5336520, DOI: 10.1161/circresaha.116.309833.Peer-Reviewed Original ResearchConceptsEndothelial cellsPostnatal cellsCell therapyDermal fibroblastsMature endothelial cellsNew vessel formationEndothelial featuresHuman endothelial cellsHindlimb ischemiaIschemic hindlimbPathophysiological investigationsEndothelial transcription factorImmature phenotypeDay 7Therapeutic potentialVascular incorporationProangiogenic effectsMature phenotypeEndothelial characteristicsIschemiaVessel formationHuman dermal fibroblastsTranscription factorsTherapyDisease investigation
2013
Trivalent Chromatin Marks the Way iN
Hysolli E, Park IH. Trivalent Chromatin Marks the Way iN. Cell Stem Cell 2013, 13: 510-512. PMID: 24209756, PMCID: PMC4665996, DOI: 10.1016/j.stem.2013.10.007.Peer-Reviewed Original ResearchNotch-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 switchTransformation 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
Excision 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 markersMutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
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. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5803-5808. PMID: 22451909, PMCID: PMC3326463, DOI: 10.1073/pnas.1202922109.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisTDP-43 proteinopathyTDP-43Human neuronsTransactive response DNA binding proteinFrontotemporal lobar degenerationFamilial amyotrophic lateral sclerosisFunctional motor neuronsCell-specific vulnerabilityTDP-43 proteinDNA binding proteinPI3K pathwayCell-autonomous phenotypeMotor neuronsLateral sclerosisStem cell linesPluripotent stem cellsGeneration of iPSCsIdentification of mutationsPluripotent stem cell lineMutant neuronsNeuronsK pathwayElevated levelsDisease mechanismsOvercoming reprogramming resistance of Fanconi anemia cells
Müller LU, Milsom MD, Harris CE, Vyas R, Brumme KM, Parmar K, Moreau LA, Schambach A, Park IH, London WB, Strait K, Schlaeger T, DeVine AL, Grassman E, D'Andrea A, Daley GQ, Williams DA. Overcoming reprogramming resistance of Fanconi anemia cells. Blood 2012, 119: 5449-5457. PMID: 22371882, PMCID: PMC3369681, DOI: 10.1182/blood-2012-02-408674.Peer-Reviewed Original ResearchConceptsFA cellsFA pathwayFA DNA repair pathwayFanconi anemiaDNA double-strand breaksFanconi anemia cellsStem cellsDNA repair pathwaysDouble-strand breaksDisease-specific iPSCsPluripotent stem cellsFuture translational applicationsGenomic integrityHuman primary cellsHematopoietic stem cellsHematopoietic differentiationChromosomal instabilityMolecular characterizationGene correctionTransgenic expressionDNA damageGenetic correctionHematopoietic cellsPrimary cellsPathway
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 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
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, Genetic
2009
Differential 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 ResearchLive 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 propertiesHuman iPS Cell Derivation/Reprogramming
Park I, Daley GQ. Human iPS Cell Derivation/Reprogramming. Current Protocols In Stem Cell Biology 2009, 8: 4a.1.1-4a.1.8. PMID: 19170021, DOI: 10.1002/9780470151808.sc04a01s8.Peer-Reviewed Original ResearchConceptsHES cellsHuman fibroblast cellsInduced pluripotent stem cellsFibroblast cellsHuman iPS cellsPluripotent stem cellsPluripotency genesTranscription factorsEmbryoid bodiesGerm layersIPS cellsStem cell culture conditionsCell coloniesCell culture conditionsStem cellsRetroviral vectorsCulture conditionsCellsReprogrammingGenesDifferentiationColoniesDissection microscope
2008
Disease-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 investigationGeneration of human-induced pluripotent stem cells
Park IH, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nature Protocols 2008, 3: 1180-1186. PMID: 18600223, DOI: 10.1038/nprot.2008.92.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsEmbryonic stem cellsIPS cellsStem cellsPatient-specific pluripotent stem cellsHuman somatic cellsInduced pluripotent stem cellsHuman iPS cellsHuman-induced pluripotent stem cellsHuman primary fibroblastsTissue replacement therapiesSomatic cellsTranscription factorsPluripotent cellsEctopic expressionRetroviral transductionSource of cellsPrimary fibroblastsHuman fibroblast lineFibroblast linesPrimary human fibroblast linesCellsInvaluable toolTransplantation of cellsImmune rejection