2024
Mechano-inhibition of endocytosis sensitizes cancer cells to Fas-induced Apoptosis
Kural M, Djakbarova U, Cakir B, Tanaka Y, Chan E, Arteaga Muniz V, Madraki Y, Qian H, Park J, Sewanan L, Park I, Niklason L, Kural C. Mechano-inhibition of endocytosis sensitizes cancer cells to Fas-induced Apoptosis. Cell Death & Disease 2024, 15: 440. PMID: 38909035, PMCID: PMC11193792, DOI: 10.1038/s41419-024-06822-3.Peer-Reviewed Original ResearchConceptsFas-induced apoptosisCell surface Fas expressionDeath receptor FasInhibition of endocytosisSurface Fas expressionPlasma membrane tensionCancer cell apoptosisEndocytosis dynamicsApoptotic signalingReceptor FasGlioblastoma cell growthFas expressionPlasma membraneCell growthEndocytosisXenograft mouse modelSoluble FasLCell apoptosisFasApoptosisRho-kinase inhibitorCancer cellsMembrane tensionNonmalignant cellsInduce tumor regressionIdentifying 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 ResearchBrain organoids: from unguided to regionalized to nucleus-specific
Xiang Y, Park I. Brain organoids: from unguided to regionalized to nucleus-specific. Life Medicine 2024, 3: lnae014. DOI: 10.1093/lifemedi/lnae014.Peer-Reviewed Original ResearchTelencephalic organoids as model systems to study cortical development and diseases
Yang W, Kiral F, Park I. Telencephalic organoids as model systems to study cortical development and diseases. Organoid 2024, 4: e1. DOI: 10.51335/organoid.2024.4.e1.Peer-Reviewed Original Research
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 technologyOrganoidsGENERATION OF BRAIN ORGANOIDS TO STUDY HUMAN BRAIN DEVELOPMENT AND DISEASES
Yang W, Park I. GENERATION OF BRAIN ORGANOIDS TO STUDY HUMAN BRAIN DEVELOPMENT AND DISEASES. IBRO Neuroscience Reports 2023, 15: s48. DOI: 10.1016/j.ibneur.2023.08.2149.Peer-Reviewed Original ResearchScalable production of tissue-like vascularized liver organoids from human PSCs
Harrison S, Siller R, Tanaka Y, Chollet M, de la Morena-Barrio M, Xiang Y, Patterson B, Andersen E, Bravo-Pérez C, Kempf H, Åsrud K, Lunov O, Dejneka A, Mowinckel M, Stavik B, Sandset P, Melum E, Baumgarten S, Bonanini F, Kurek D, Mathapati S, Almaas R, Sharma K, Wilson S, Skottvoll F, Boger I, Bogen I, Nyman T, Wu J, Bezrouk A, Cizkova D, Corral J, Mokry J, Zweigerdt R, Park I, Sullivan G. Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental & Molecular Medicine 2023, 55: 2005-2024. PMID: 37653039, PMCID: PMC10545717, DOI: 10.1038/s12276-023-01074-1.Peer-Reviewed Original ResearchConceptsExtracellular matrixSingle-cell RNA sequencingBasic developmental biologyEmbryonic liver developmentPost-translational modificationsLiver-like functionsCostly growth factorsOrganoid modelsKey liver functionsCellular diversityCellular repertoireDevelopmental biologyCellular complexityN-glycosylationRNA sequencingDe novo vascularizationNumber of tissuesProtein productionSerum protein productionLiver developmentHuman PSCsDrug toxicity assessmentOrganoidsSmall moleculesGrowth factorFemale 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 developmentPTCHD1NucleusKinaseGenesSequencingMutations 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
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformationsAdvanced 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 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 ResearchLive isolation of naïve ESCs via distinct glucose metabolism and stored glycogen
Kim KT, Oh JY, Park S, Kim SM, Benjamin P, Park IH, Chun KH, Chang YT, Cha HJ. Live isolation of naïve ESCs via distinct glucose metabolism and stored glycogen. Metabolic Engineering 2022, 72: 97-106. PMID: 35283260, DOI: 10.1016/j.ymben.2022.03.003.Peer-Reviewed Original ResearchRegion Specific Brain Organoids to Study Neurodevelopmental Disorders
Susaimanickam PJ, Kiral FR, Park IH. Region Specific Brain Organoids to Study Neurodevelopmental Disorders. International Journal Of Stem Cells 2022, 15: 26-40. PMID: 35220290, PMCID: PMC8889336, DOI: 10.15283/ijsc22006.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
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 Research