2024
Identifying an Early Neuropathological Mechanism in Schizophrenia With Brain Organoids
Kim J, Park I. Identifying an Early Neuropathological Mechanism in Schizophrenia With Brain Organoids. Biological Psychiatry 2024, 95: 608-610. PMID: 38479977, DOI: 10.1016/j.biopsych.2024.01.015.Peer-Reviewed Original Research
2023
Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation
Sun J, Osenberg S, Irwin A, Ma L, Lee N, Xiang Y, Li F, Wan Y, Park I, Maletic-Savatic M, Ballas N. Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation. Cell Reports 2023, 42: 111942. PMID: 36640327, PMCID: PMC10857774, DOI: 10.1016/j.celrep.2022.111942.Peer-Reviewed Original ResearchConceptsMECP2 mutationsTranscriptional regulator MeCP2Rett syndromeTranscriptional landscapeTranscriptional changesDysfunctional mitochondriaHuman astrocytesAstrocyte gene expressionGene expressionMECP2 geneMolecular signaturesMutationsPost-natal maturationMaturationDevelopmental maturationBrain bioenergeticsMolecular featuresFunctional maturationStellate morphologyMature morphologyMetabolic aberrationsHuman-based modelsAstrocytesKey roleNeurodevelopmental disorders
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 ResearchGetting the right cells
Cakir B, Park IH. Getting the right cells. ELife 2022, 11: e80373. PMID: 35770899, PMCID: PMC9246363, DOI: 10.7554/elife.80373.Peer-Reviewed Original Research
2021
Exploration of alcohol use disorder-associated brain miRNA–mRNA regulatory networks
Lim Y, Beane-Ebel JE, Tanaka Y, Ning B, Husted CR, Henderson DC, Xiang Y, Park IH, Farrer LA, Zhang H. Exploration of alcohol use disorder-associated brain miRNA–mRNA regulatory networks. Translational Psychiatry 2021, 11: 504. PMID: 34601489, PMCID: PMC8487426, DOI: 10.1038/s41398-021-01635-w.Peer-Reviewed Original ResearchRegional specification and complementation with non-neuroectodermal cells in human brain organoids
Tanaka Y, Park IH. Regional specification and complementation with non-neuroectodermal cells in human brain organoids. Journal Of Molecular Medicine 2021, 99: 489-500. PMID: 33651139, PMCID: PMC8026433, DOI: 10.1007/s00109-021-02051-9.Peer-Reviewed Original ResearchAnimalsBrainCellular Reprogramming TechniquesEmbryoid BodiesEndothelial CellsFetusFibroblast Growth Factor 2Hedgehog ProteinsHuman Umbilical Vein Endothelial CellsHumansInduced Pluripotent Stem CellsIntercellular Signaling Peptides and ProteinsMicrogliaNeuronsOrgan SpecificityOrganogenesisOrganoidsRetinaSpinal CordWnt Signaling Pathway
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisDeconstructing and reconstructing the human brain with regionally specified brain organoids
Xiang Y, Cakir B, Park IH. Deconstructing and reconstructing the human brain with regionally specified brain organoids. Seminars In Cell And Developmental Biology 2020, 111: 40-51. PMID: 32553582, DOI: 10.1016/j.semcdb.2020.05.023.Peer-Reviewed Original ResearchDysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons
Xiang Y, Tanaka Y, Patterson B, Hwang SM, Hysolli E, Cakir B, Kim KY, Wang W, Kang YJ, Clement EM, Zhong M, Lee SH, Cho YS, Patra P, Sullivan GJ, Weissman SM, Park IH. Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons. Molecular Cell 2020, 79: 84-98.e9. PMID: 32526163, PMCID: PMC7375197, DOI: 10.1016/j.molcel.2020.05.016.Peer-Reviewed Original ResearchConceptsMECP2 mutant neuronsEnhancer-promoter interactionsRett syndromeRTT-like phenotypesChromatin bindingMeCP2 functionMethyl-CpGAbnormal transcriptionRTT etiologyMutant neuronsBET inhibitorsPotential therapeutic opportunitiesMECP2 mutationsProtein 2Human brain organoidsFunctional phenotypeJQ1BRD4Therapeutic opportunitiesBrain organoidsFunction underliesMutationsPhenotypeHuman brain culturesCritical driverSynthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain
Tanaka Y, Cakir B, Xiang Y, Sullivan GJ, Park IH. Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain. Cell Reports 2020, 30: 1682-1689.e3. PMID: 32049002, PMCID: PMC7043376, DOI: 10.1016/j.celrep.2020.01.038.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 deliveryCellsEndotheliumMicrovasculature
2018
Generation and Fusion of Human Cortical and Medial Ganglionic Eminence Brain Organoids
Xiang Y, Yoshiaki T, Patterson B, Cakir B, Kim K, Cho YS, Park I. Generation and Fusion of Human Cortical and Medial Ganglionic Eminence Brain Organoids. Current Protocols In Stem Cell Biology 2018, 47 PMID: 30854156, PMCID: PMC6402040, DOI: 10.1002/cpsc.61.Peer-Reviewed Original ResearchConceptsMedial ganglionic eminenceBrain organoidsBrain regionsBrain developmentSpecific brain regionsDifferent brain regionsHuman CorticalHuman brain developmentCortical organoidsGanglionic eminenceNeurological disordersInterneuron migrationSpecific regionalizationOrganoid culturesOrganoidsBrain organoid culture
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
2011
Induced pluripotent stem cell models from X‐linked adrenoleukodystrophy patients
Jang J, Kang H, Kim H, Kim JY, Huh YJ, Kim D, Yoo J, Lee J, Lim B, Lee J, Yoon T, Park I, Hwang D, Daley GQ, Kim D. Induced pluripotent stem cell models from X‐linked adrenoleukodystrophy patients. Annals Of Neurology 2011, 70: 402-409. PMID: 21721033, DOI: 10.1002/ana.22486.Peer-Reviewed Original ResearchMeSH KeywordsAdrenoleukodystrophyATP Binding Cassette Transporter, Subfamily DATP-Binding Cassette TransportersBrainCell DifferentiationDNAExcitatory Postsynaptic PotentialsFatty Acids, NonesterifiedHematopoietic Stem Cell TransplantationHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInduced Pluripotent Stem CellsLovastatinNeuronsOligodendrogliaPhenotypePhenylbutyratesReverse Transcriptase Polymerase Chain ReactionConceptsChildhood cerebral ALDX-ALDVLCFA accumulationLong chain fatty acid levelsAppropriate animal model systemsSevere clinical manifestationsFatty acid levelsAnimal model systemsDisease-relevant phenotypesClinical manifestationsCerebral ALDABCD1 mutationsAdrenoleukodystrophy patientsDevelopment of therapeuticsHuman oligodendrocytesUnique cellular modelDisease subtypesAbnormal accumulationAccurate diagnosisPluripotent stem cell modelsOligodendrocytesNew therapeuticsAcid levelsOligodendrocyte differentiationStem cell model