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
2020
Dysregulation 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 driver
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 ResearchMeSH KeywordsAnimalsBlood-Brain BarrierBrainCells, CulturedHuman Embryonic Stem CellsHumansMiceOrganoidsSingle-Cell AnalysisTissue EngineeringTranscription FactorsConceptsHuman 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
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 ResearchMeSH KeywordsCellular ReprogrammingDNA MethylationEpigenesis, GeneticHuman Embryonic Stem CellsHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4MicroRNAsConceptsDNA 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
2015
Transcriptional 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