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 statusCells
2022
A nomenclature consensus for nervous system organoids and assembloids
Pașca SP, Arlotta P, Bateup HS, Camp JG, Cappello S, Gage FH, Knoblich JA, Kriegstein AR, Lancaster MA, Ming GL, Muotri AR, Park IH, Reiner O, Song H, Studer L, Temple S, Testa G, Treutlein B, Vaccarino FM. A nomenclature consensus for nervous system organoids and assembloids. Nature 2022, 609: 907-910. PMID: 36171373, PMCID: PMC10571504, DOI: 10.1038/s41586-022-05219-6.Peer-Reviewed Original Research
2020
Generation of Regionally Specified Human Brain Organoids Resembling Thalamus Development
Xiang Y, Cakir B, Park IH. Generation of Regionally Specified Human Brain Organoids Resembling Thalamus Development. STAR Protocols 2020, 1: 100001. PMID: 33103124, PMCID: PMC7580078, DOI: 10.1016/j.xpro.2019.100001.Peer-Reviewed Original Research
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 embryosEnhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel
Lee SJ, Sohn YD, Andukuri A, Kim S, Byun J, Han JW, Park IH, Jun HW, Yoon YS. Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel. Circulation 2017, 136: 1939-1954. PMID: 28972000, PMCID: PMC5685906, DOI: 10.1161/circulationaha.116.026329.Peer-Reviewed Original ResearchConceptsCell survivalHPSC-ECsHuman pluripotent stem cell-derived endothelial cellsEndothelial lineage differentiationGlycogen synthase kinase-3β inhibitorHuman pluripotent stem cellsStem cell-derived endothelial cellsGrowth factorDifferentiation of hPSCsLonger cell survivalEndothelial cellsCell-derived endothelial cellsVessel formationPluripotent stem cell-derived endothelial cellsBetter perfusion recoveryPluripotent stem cellsNanomatrix gelLong-term cell survivalMesodermal lineagesLineage differentiationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsDifferentiation systemFibroblast growth factorBasic fibroblast growth factorFusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration
Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, Cakir B, Kim KY, Lombroso AP, Hwang SM, Zhong M, Stanley EG, Elefanty AG, Naegele JR, Lee SH, Weissman SM, Park IH. Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration. Cell Stem Cell 2017, 21: 383-398.e7. PMID: 28757360, PMCID: PMC5720381, DOI: 10.1016/j.stem.2017.07.007.Peer-Reviewed Original ResearchConceptsHuman brain developmentChromatin accessibility dynamicsTransposase-accessible chromatinHigh-throughput sequencing analysisRegion-specific organoidsHuman pluripotent stem cellsRNA sequencing profilingHuman interneuron migrationPluripotent stem cellsRelated lineagesBrain developmentAccessibility dynamicsBulk assaysInterneuron migrationLineage relationshipsOrganoid techniquesSequencing profilingSequencing analysisFunctional neuronsOrganoid developmentStem cellsCortical organoidsOrganoidsBrain organoidsMGEGenetic 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
2015
Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming
Tanaka Y, Hysolli E, Su J, Xiang Y, Kim KY, Zhong M, Li Y, Heydari K, Euskirchen G, Snyder MP, Pan X, Weissman SM, Park IH. Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming. Stem Cell Reports 2015, 4: 1125-1139. PMID: 26004630, PMCID: PMC4471828, DOI: 10.1016/j.stemcr.2015.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceCellular ReprogrammingCyclin EEmbryonic Stem CellsGene Expression RegulationHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMolecular Sequence DataOctamer Transcription Factor-3Oncogene ProteinsPolymorphism, Single NucleotidePrincipal Component AnalysisProto-Oncogene Proteins c-mycRNASequence Analysis, RNASOXB1 Transcription FactorsTranscriptomeConceptsHuman somatic cell reprogrammingMonoallelic gene expressionSomatic cell reprogrammingPrevious transcriptome studiesHuman iPSC reprogrammingPluripotent stem cellsCell reprogrammingIPSC reprogrammingTranscriptome dataEarly reprogrammingTranscriptome studiesTranscriptome changesBiallelic expressionRNA-seqSomatic cellsExpression analysisGene expressionSpliced formsReprogrammingTranscriptome signaturesStem cellsInvaluable resourceCellular surface markersBiomedical researchCellsRole 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 ResearchConceptsMES 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
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
Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2)
Tanaka Y, Kim KY, Zhong M, Pan X, Weissman SM, Park IH. Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2). Human Molecular Genetics 2013, 23: 1045-1055. PMID: 24129406, PMCID: PMC3900111, DOI: 10.1093/hmg/ddt500.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsMutant MECP2X chromosomeMethyl-CpGStem cellsGene expressionLong-range chromatin interactionsFundamental cellular physiologyRett syndromeMitochondrial membrane proteinInactive X chromosomeProtein 2Chromatin interactionsTranscriptional regulationTranscription regulatorsCellular physiologyTranscriptome analysisLoss of functionMembrane proteinsMeCP2 resultsDe novo mutationsRegulatory mechanismsMeCP2ChromosomesRTT patientsInvestigation 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 modelRecapitulationMaintenanceIdentificationTherapeutic 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 modelsNotch-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 expressionModelling human disease with pluripotent stem cells.
Siller R, Greenhough S, Park IH, Sullivan GJ. Modelling human disease with pluripotent stem cells. Current Gene Therapy 2013, 13: 99-110. PMID: 23444871, PMCID: PMC3785403, DOI: 10.2174/1566523211313020004.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsStem cellsAffected cell typesCellular reprogrammingEndodermal lineagesPluripotent cellsHuman diseasesCell typesGenetic diseasesDisease phenotypeDisease mechanismsDisease modellingTissue of interestPatient tissuesCellsLimitless supplyReprogrammingLineagesRecent progressProgenyPhenotypeTissueTherapeutic interventionsHigh levelsCell technology
2012
A Dual Role of Evi-1 During Developmental Hematopoiesis
Konantz M, Grauer M, Grzywna S, Park I, Daley G, Kanz L, Lengerke C. A Dual Role of Evi-1 During Developmental Hematopoiesis. Blood 2012, 120: 765. DOI: 10.1182/blood.v120.21.765.765.Peer-Reviewed Original ResearchEvi-1Developmental hematopoiesisZebrafish embryosSCL expressionProgenitor cellsHematopoietic cellsPre-mRNA splicingHuman hematopoietic developmentEvi-1 locusMurine hematopoietic cellsHuman iPS cellsPrecise molecular basisSurvival/proliferationEmbryonic myelopoiesisPluripotent stem cellsEvi-1 expressionErythroid progenitor cellsDefinitive hematopoiesisPrimitive erythroid progenitor cellsPrimitive erythropoiesisZebrafish zygotesHSC formationPrimitive hematopoiesisBlood developmentSitu hybridization analysis