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
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 ResearchConceptsHuman 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 deliveryCellsEndotheliumMicrovasculatureThe 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 cellsPluripotencyExosomesDifferentiationRNAhESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
Xiang Y, Tanaka Y, Cakir B, Patterson B, Kim KY, Sun P, Kang YJ, Zhong M, Liu X, Patra P, Lee SH, Weissman SM, Park IH. hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids. Cell Stem Cell 2019, 24: 487-497.e7. PMID: 30799279, PMCID: PMC6853597, DOI: 10.1016/j.stem.2018.12.015.Peer-Reviewed Original ResearchConceptsReciprocal projectionsThree-dimensional organoid modelsForebrain disorderHuman brain developmentCortical organoidsHuman thalamusPeripheral tissuesThalamusRelated disordersThalamic developmentSingle-cell RNA sequencingBrain developmentHuman embryonic stem cellsCircuit organizationCortexOrganoid modelsRegion-specific organoidsTelencephalic fateStem cellsOrganoid techniquesOrganoidsDisordersRNA sequencingRelay hubDisease
2013
Pluripotent 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 expression
2012
Reprogramming 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
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 vector
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 genesHematopoietic Development from Human Induced Pluripotent Stem Cells
Lengerke C, Grauer M, Niebuhr NI, Riedt T, Kanz L, Park I, Daley GQ. Hematopoietic Development from Human Induced Pluripotent Stem Cells. Annals Of The New York Academy Of Sciences 2009, 1176: 219-227. PMID: 19796250, PMCID: PMC2849804, DOI: 10.1111/j.1749-6632.2009.04606.x.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsMouse embryonic stem cellsPluripotent stem cellsHematopoietic developmentInduced pluripotent stem cellsHuman induced pluripotent stem cellsHematopoietic stem cellsStem cellsDifferentiated somatic cellsHuman embryonic stem cellsHuman hematopoietic developmentStem cell linesGene expression dataIrradiated adult miceHox genesPluripotent stateBlood lineagesSomatic cellsEctopic expressionCombinatorial overexpressionExpression dataBlood formationIPS cellsColony activityMultilineage reconstitutionGeneration of induced pluripotent stem cells from human blood
Loh YH, Agarwal S, Park IH, Urbach A, Huo H, Heffner GC, Kim K, Miller JD, Ng K, Daley GQ. Generation of induced pluripotent stem cells from human blood. Blood 2009, 113: 5476-5479. PMID: 19299331, PMCID: PMC2689048, DOI: 10.1182/blood-2009-02-204800.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsPluripotent cell-specific genesPatient-specific stem cellsTranscription factorsStem cellsHuman embryonic stem cellsPluripotency-associated transcription factorsEmbryonic stem cellsCell-specific genesInduced pluripotent stem cellsDNA methylation statusEctopic expressionHematopoietic lineagesRetroviral transductionMethylation statusSomatic mutationsHuman dermal fibroblastsHuman bloodDermal fibroblastsCellsHuman peripheral blood cellsExpressionPluripotencyPeripheral blood cellsLineages