2023
Generation 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
Expression 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 deliveryCellsEndotheliumMicrovasculaturehESC-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
Fusion 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 organoidsMGE
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 analysisReprogrammingDNA methylation on N6-adenine in mammalian embryonic stem cells
Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ. DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 2016, 532: 329-333. PMID: 27027282, PMCID: PMC4977844, DOI: 10.1038/nature17640.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlkB Homolog 1, Histone H2a DioxygenaseAnimalsCell DifferentiationDNA MethylationDNA Transposable ElementsDNA-(Apurinic or Apyrimidinic Site) LyaseEnhancer Elements, GeneticEpigenesis, GeneticEvolution, MolecularGene SilencingLong Interspersed Nucleotide ElementsMammalsMiceMouse Embryonic Stem CellsUp-RegulationX ChromosomeConceptsLINE-1 transposonsEmbryonic stem cellsN6-methyladenineMammalian genomesEpigenetic silencingDNA methylationX chromosomeMammalian embryonic stem cellsEmbryonic stem cell differentiationMouse embryonic stem cellsStem cellsStem cell differentiationMammalian evolutionTranscriptional silencingEvolutionary ageGene activationDNA modificationsL1 elementsCell differentiationSilencingTransposonN6-adenineGenomeActivation signalsChromosomes
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 researchCellsTranscriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells
Tadeu AM, Lin S, Hou L, Chung L, Zhong M, Zhao H, Horsley V. Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells. PLOS ONE 2015, 10: e0122493. PMID: 25849374, PMCID: PMC4388500, DOI: 10.1371/journal.pone.0122493.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsEmbryonic stem cellsEctoderm specificationStem cellsHuman embryonic stem cell differentiationEmbryonic stem cell differentiationStem cell differentiationKeratinocyte fateEctoderm lineageEpidermal specificationTranscriptional regulationCandidate regulatorsTranscriptional profilingEpidermal developmentGrowth factor activityProtein aP2Keratinocyte developmentCell differentiationΓ-secretase inhibitor DAPTGenesFactor activityHomeostatic conditionsEpithelial tissuesInhibitor DAPTCell signature
2014
Histone Variant H2A.X Deposition Pattern Serves as a Functional Epigenetic Mark for Distinguishing the Developmental Potentials of iPSCs
Wu T, Liu Y, Wen D, Tseng Z, Tahmasian M, Zhong M, Rafii S, Stadtfeld M, Hochedlinger K, Xiao A. Histone Variant H2A.X Deposition Pattern Serves as a Functional Epigenetic Mark for Distinguishing the Developmental Potentials of iPSCs. Cell Stem Cell 2014, 15: 281-294. PMID: 25192463, DOI: 10.1016/j.stem.2014.06.004.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsLineage gene expressionHistone variant H2A.XCell lineage commitmentDevelopmental potentialMouse iPSC linesIPSC linesPluripotent stem cell (iPSC) technologyEpigenetic marksLineage genesEpigenetic mechanismsLineage commitmentLineage differentiationExtraembryonic differentiationStem cell technologyGene expressionTetraploid complementationIPSC clonesIPSC qualityStem cellsFunctional markersH2A.XDifferentiationIPSCsComplementationUsing Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells
Tseng Z, Wu T, Liu Y, Zhong M, Xiao A. Using Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells. Methods In Molecular Biology 2014, 1176: 11-22. PMID: 25030915, DOI: 10.1007/978-1-4939-0992-6_2.Peer-Reviewed Original ResearchConceptsNative chromatin immunoprecipitationHigh-throughput sequencingEmbryonic stem cellsChromatin immunoprecipitationHistone variantsMouse embryonic stem cellsGenome-wide localizationChromatin-associated factorsStem cellsProtein of interestMassive parallel sequencingHistone modificationsChromatin regionsChromatin pelletEpigenetic techniquesDNA fragmentsParallel sequencingImmunoprecipitationLibrary constructionSequencingEnzymatic digestionProtein depositionCellsH2A.XSpecific antibodies
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 patients
2010
The Yb Body, a Major Site for Piwi-associated RNA Biogenesis and a Gateway for Piwi Expression and Transport to the Nucleus in Somatic Cells*
Qi H, Watanabe T, Ku HY, Liu N, Zhong M, Lin H. The Yb Body, a Major Site for Piwi-associated RNA Biogenesis and a Gateway for Piwi Expression and Transport to the Nucleus in Somatic Cells*. Journal Of Biological Chemistry 2010, 286: 3789-3797. PMID: 21106531, PMCID: PMC3030380, DOI: 10.1074/jbc.m110.193888.Peer-Reviewed Original ResearchConceptsYb bodiesSomatic cellsPiRNA pathwayGerm lineEndo-siRNA pathwaySomatic niche cellsTudor-like domainGonadal somatic cellsPutative RNA helicaseCo-immunoprecipitation experimentsSomatic stem cellsFlamenco locusSomatic piRNAsPiRNA biogenesisEndo-siRNAsRNA biogenesisRNA pathwaysPiwi expressionRNA helicaseNovel proteinPiwiNiche cellsMolecular basisStem cellsBiogenesis