2020
Reprogramming progressive cells display low CAG promoter activity
Hu X, Wu Q, Zhang J, Kim J, Chen X, Hartman AA, Eastman AE, Park I, Guo S. Reprogramming progressive cells display low CAG promoter activity. Stem Cells 2020, 39: 43-54. PMID: 33075202, PMCID: PMC7821215, DOI: 10.1002/stem.3295.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCellular ReprogrammingCellular Reprogramming TechniquesMiceMice, TransgenicPromoter Regions, GeneticTranscription FactorsDysregulation 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
2019
Engineering of human brain organoids with a functional vascular-like system
Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ, Chapeton K, Patterson B, Yuan Y, He CS, Raredon MSB, Dengelegi J, Kim KY, Sun P, Zhong M, Lee S, Patra P, Hyder F, Niklason LE, Lee SH, Yoon YS, Park IH. Engineering of human brain organoids with a functional vascular-like system. Nature Methods 2019, 16: 1169-1175. PMID: 31591580, PMCID: PMC6918722, DOI: 10.1038/s41592-019-0586-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood-Brain BarrierBrainCells, CulturedHuman Embryonic Stem CellsHumansMiceOrganoidsSingle-Cell AnalysisTissue EngineeringTranscription FactorsConceptsHuman cortical organoidsBlood-brain barrier characteristicsTrans-endothelial electrical resistanceVasculature-like structuresHuman brain organoidsHuman brain developmentCortical organoidsFunctional maturationPrenatal brainBrain diseasesBrain developmentHuman embryonic stem cellsBlood vesselsBrain organoidsTight junctionsDiseaseStem cellsOrganoidsVariant 2Nutrient transportersNutrient deliveryCellsEndotheliumMicrovasculature
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 investigationSingle 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
Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery
Greer CB, Tanaka Y, Kim YJ, Xie P, Zhang MQ, Park IH, Kim TH. Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery. Cell Reports 2015, 13: 1444-1455. PMID: 26549458, PMCID: PMC4934896, DOI: 10.1016/j.celrep.2015.10.013.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCell Cycle ProteinsCell Line, TumorEpigenesis, GeneticHistone Deacetylase InhibitorsHistone DeacetylasesHSP90 Heat-Shock ProteinsHumansKineticsNuclear ProteinsProtein BindingProtein Processing, Post-TranslationalRNA Polymerase IITranscription Elongation, GeneticTranscription FactorsConceptsNegative elongation factorElongation factorEnhancer activityHeat shock protein 90 (HSP90) activityEnhancer RNA productionRNA polymerase IISame genomic siteElongation machinerySmall molecule inhibitorsGene bodiesTranscription elongationPolymerase IINascent transcriptionGenomic sitesIntergenic regionGene activationRNA productionEfficient elongationMolecule inhibitorsProtein 4TranscriptionPromoterHDACsEnhancerElongationRole 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
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
A 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 FactorsTransgenes
2008
Generation 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 ResearchMeSH KeywordsCell Culture TechniquesFibroblastsHumansKruppel-Like Factor 4Pluripotent Stem CellsRetroviridaeTranscription FactorsTransduction, GeneticConceptsPluripotent 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
2007
Reprogramming of human somatic cells to pluripotency with defined factors
Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2007, 451: 141-146. PMID: 18157115, DOI: 10.1038/nature06534.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCell DifferentiationCell ShapeCells, CulturedDNA MethylationDNA-Binding ProteinsEmbryonic Stem CellsFetusFibroblastsGene Expression ProfilingHMGB ProteinsHomeodomain ProteinsHumansInfant, NewbornKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsPromoter Regions, GeneticProto-Oncogene Proteins c-mycSOXB1 Transcription FactorsTeratomaTranscription FactorsTransplantation, HeterologousConceptsEmbryonic stem cellsStem cellsIPS cellsHuman somatic cellsInduced pluripotent stem cellsHuman iPS cellsPluripotent stem cellsHuman primary cellsPatient-specific cellsEarly embryosTranscription factorsSomatic cellsEctopic expressionPluripotencyGene expressionHuman cellsMurine fibroblastsDefined factorsPrimary cellsCell linesDermal fibroblastsCellsInvaluable toolFibroblastsExpressionDebugging cellular reprogramming
Park IH, Daley GQ. Debugging cellular reprogramming. Nature Cell Biology 2007, 9: 871-873. PMID: 17671453, DOI: 10.1038/ncb0807-871.Peer-Reviewed Original Research