2023
Diencephalic organoids – A key to unraveling development, connectivity, and pathology of the human diencephalon
Kiral F, Choe M, Park I. Diencephalic organoids – A key to unraveling development, connectivity, and pathology of the human diencephalon. Frontiers In Cellular Neuroscience 2023, 17: 1308479. PMID: 38130869, PMCID: PMC10733522, DOI: 10.3389/fncel.2023.1308479.Peer-Reviewed Original ResearchHuman diencephalonBrain organoidsNeurodevelopmental disordersDevelopmental brain disordersHuman brain tissueThalamocortical connectionsBrain disordersDiencephalic developmentBrain tissueDiencephalic structuresOrganoid modelsHuman-specific aspectsSensory processingDiencephalonDisordersTelencephalic fatePathologyStem cellsStem cell technologyOrganoidsFemale 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
Advanced in vitro models: Microglia in action
Cakir B, Kiral F, Park I. Advanced in vitro models: Microglia in action. Neuron 2022, 110: 3444-3457. PMID: 36327894, DOI: 10.1016/j.neuron.2022.10.004.Peer-Reviewed Original ResearchA 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 ResearchDyslexia 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 migrationHESCsGenesLociHuman Down syndrome microglia are up for a synaptic feast
Kiral FR, Park IH. Human Down syndrome microglia are up for a synaptic feast. Cell Stem Cell 2022, 29: 1007-1008. PMID: 35803219, DOI: 10.1016/j.stem.2022.06.008.Peer-Reviewed Original ResearchExpression 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
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
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
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 embryosFusion 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 organoidsMGEBisulfite-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
Single 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 factorsDnmt1 regulates the myogenic lineage specification of muscle stem cells
Liu R, Kim KY, Jung YW, Park IH. Dnmt1 regulates the myogenic lineage specification of muscle stem cells. Scientific Reports 2016, 6: 35355. PMID: 27752090, PMCID: PMC5082760, DOI: 10.1038/srep35355.Peer-Reviewed Original ResearchConceptsImportant epigenetic markKnockout mouse approachesDNA methylation patternsMuscle stem cellsDaughter DNA strandsDNMT1 regulationEpigenetic marksLineage specificationCellular identityDNA methylationMethylation patternsDNMT1 depletionMyogenic genesMyogenic differentiationLineage fidelityNegative regulatorGene expressionDNMT1Osteogenic lineageFunctional roleFunctional consequencesMouse approachDNA strandsId-1Stem cellsNeural Stem Cells Restore Hair Growth through Activation of the Hair Follicle Niche
Hwang I, Choi KA, Park HS, Jeong H, Kim JO, Seol KC, Kwon HJ, Park IH, Hong S. Neural Stem Cells Restore Hair Growth through Activation of the Hair Follicle Niche. Cell Transplantation 2016, 25: 1439-1451. PMID: 27110030, DOI: 10.3727/096368916x691466.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor-1Shaven dorsal skinNeural stem cellsVascular endothelial growth factorDermal papilla cellsHepatocyte growth factorKeratinocyte growth factorGrowth factorHair follicle nicheHair growthDorsal skinStem cellsAnagen phaseGrowth factor-1Endothelial growth factorGrowth factor pathwaysCombined growth factorsMolecular signaling pathwaysPharmacological therapyHair regrowthHair shaft lengthBone morphogenetic protein family membersNSC treatmentProtein family membersHair follicle stem cellsRegulation 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