2023
Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations
Patterson B, Yang B, Tanaka Y, Kim K, Cakir B, Xiang Y, Kim J, Wang S, Park I. Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations. Science Advances 2023, 9: eadf2245. PMID: 37540754, PMCID: PMC10403202, DOI: 10.1126/sciadv.adf2245.Peer-Reviewed Original ResearchConceptsNaïve human pluripotent stem cellsHuman pluripotent stem cellsX-chromosome inactivationX chromosomePluripotent stem cellsStem cellsNaïve human embryonic stem cellsX chromosome stateX chromosome statusInactive X chromosomeActive X chromosomeHuman embryonic stem cellsEarly embryonic cellsEmbryonic stem cellsUnique epigenetic regulationChromatin compactionGenomic resolutionEpigenetic regulationChromosome inactivationChromosome stateSomatic cellsEmbryonic cellsChromosomesChromosome statusCellsGeneration of ventralized human thalamic organoids with thalamic reticular nucleus
Kiral F, Cakir B, Tanaka Y, Kim J, Yang W, Wehbe F, Kang Y, Zhong M, Sancer G, Lee S, Xiang Y, Park I. Generation of ventralized human thalamic organoids with thalamic reticular nucleus. Cell Stem Cell 2023, 30: 677-688.e5. PMID: 37019105, PMCID: PMC10329908, DOI: 10.1016/j.stem.2023.03.007.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsSingle-cell RNA sequencingReceptor tyrosine protein kinaseTyrosine protein kinaseEmbryonic stem cellsDisease-associated genesLineage developmentRNA sequencingHuman brain developmentOrganoid systemsStem cellsHuman brain organoidsNeuronal functionBrain organoidsOrganoidsBrain organoid systemsDistinct nucleiBrain developmentThalamic developmentPTCHD1NucleusKinaseGenesSequencing
2022
Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development
Paniagua S, Cakir B, Hu Y, Kiral FR, Tanaka Y, Xiang Y, Patterson B, Gruen JR, Park IH. Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development. Frontiers In Cell And Developmental Biology 2022, 10: 967147. PMID: 36016658, PMCID: PMC9395643, DOI: 10.3389/fcell.2022.967147.Peer-Reviewed Original ResearchHuman embryonic stem cellsEmbryonic stem cellsGenetic linkage analysisNeuroepithelial cell differentiationHESC differentiationRegulatory elementsChromosome 6p22Human cortical developmentCell cycleMolecular mechanismsAssociation studiesCell developmentCell differentiationLinkage analysisNeuronal migrationStem cellsDYX2 locusCortical developmentNeuroectodermal differentiationDifferentiationGene KIAA0319Radial migrationHESCsGenesLociExpression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids
Cakir B, Tanaka Y, Kiral FR, Xiang Y, Dagliyan O, Wang J, Lee M, Greaney AM, Yang WS, duBoulay C, Kural MH, Patterson B, Zhong M, Kim J, Bai Y, Min W, Niklason LE, Patra P, Park IH. Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids. Nature Communications 2022, 13: 430. PMID: 35058453, PMCID: PMC8776770, DOI: 10.1038/s41467-022-28043-y.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsHuman cortical organoidsTranscription factor PUSingle-cell RNA sequencingMicroglia-like cellsSingle-cell transcriptomicsEmbryonic stem cellsDisease stage IIIRole of microgliaAD-associated genesExpression of genesCortical organoidsNeurodegenerative disordersRNA sequencingMolecular damageIntact complementStem cellsDysfunction of microgliaFunctional microgliaReduced expressionGenesCell clustersExpressionChemokine systemHuman microglia
2019
The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
Belair C, Sim S, Kim KY, Tanaka Y, Park IH, and, Wolin SL. The RNA exosome nuclease complex regulates human embryonic stem cell differentiation. Journal Of Cell Biology 2019, 218: 2564-2582. PMID: 31308215, PMCID: PMC6683745, DOI: 10.1083/jcb.201811148.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCross-Linking ReagentsEndodermExosome Multienzyme Ribonuclease ComplexForkhead Transcription FactorsGene Expression RegulationHeLa CellsHuman Embryonic Stem CellsHumansLong Interspersed Nucleotide ElementsMesodermMicroRNAsPhenotypeRNARNA, Long NoncodingRNA, MessengerRNA, Small InterferingTranscription, GeneticTransgenesConceptsEmbryonic stem cellsESC differentiationTranscription networksSurveillance pathwayHuman embryonic stem cell differentiationGerm layersEmbryonic stem cell differentiationHuman embryonic stem cellsHuman ESC differentiationLINE-1 retrotransposonsStem cell differentiationTranscription factor crucialDevelopmental regulatorsMesendoderm formationDevelopmental genesRNA decayTranscription factorsSpecific miRNAsCell differentiationFactor crucialStem cellsPluripotencyExosomesDifferentiationRNA
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
New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology
Patterson B, Tanaka Y, Park IH. New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology. Tissue Engineering And Regenerative Medicine 2017, 14: 643-652. PMID: 29276809, PMCID: PMC5738034, DOI: 10.1007/s13770-017-0096-4.Peer-Reviewed Original ResearchPluripotent stem cellsX chromosome statusStem cell biologyCell biologyX chromosome dosage compensationStem cellsDosage compensation processX-chromosome regulationChromosome dosage compensationHuman PSCsCell fate determinationActive X chromosomeChromosome statusEmbryonic stem cellsHuman pluripotent stem cellsHuman preimplantation embryosSpecific lincRNAsDosage compensationChromosome architectureChromosome regulationFate determinationImprinting statusEpigenetic dysregulationX chromosomePreimplantation embryos
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
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 ResearchConceptsX 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
Investigation 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 ResearchConceptsPluripotent stem cellsStem cellsRett syndromeFunction of MeCP2Pathophysiology of RTTEmbryonic stem cellsEpigenetic instabilityTranscription factorsDe novo mutationsRTT phenotypeCurrent iPSCHuman diseasesMeCP2Novo mutationsIPSCsCellsNeurodevelopmental disordersOverexpressionMutationsPhenotypeMurine modelRecapitulationMaintenanceIdentificationPluripotent 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 ResearchReprogramming 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
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 cellsInduced pluripotent stem cells for neural tissue engineering
Wang A, Tang Z, Park IH, Zhu Y, Patel S, Daley GQ, Li S. Induced pluripotent stem cells for neural tissue engineering. Biomaterials 2011, 32: 5023-5032. PMID: 21514663, PMCID: PMC3100451, DOI: 10.1016/j.biomaterials.2011.03.070.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsTissue engineeringNeural tissue engineeringPluripotent stem cellsNanofibrous tubular scaffoldsRegenerative medicine applicationsStem cellsTissue-engineered nerve conduitNeural crest stem cellsDifferentiation of iPSCsTeratoma formationMedicine applicationsGreat promiseTremendous potentialIPSC differentiationEctodermal lineagesTubular scaffoldsMultipotent neural crest stem cellsCell therapyEngineeringHuman iPSCDifferent cell linesAccelerated regenerationScaffoldsIPSCs
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 differencesHESCs
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 genesDifferential 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