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
2020
Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions
McKnight I, Hart C, Park IH, Shim JW. Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions. Experimental Neurology 2020, 335: 113523. PMID: 33157092, PMCID: PMC7750280, DOI: 10.1016/j.expneurol.2020.113523.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCentral nervous systemFamilial Parkinson's diseaseAlzheimer's diseaseCausative genesGenome Data ViewerHuman genetic mutationsDisease-susceptible genesHigh mutation rateGenetic mutationsHuman congenital hydrocephalusHuman clinical studiesPutative genesHuman genesGenomic informationT contentChromosomal characteristicsDNA compositionGenetic basisHigh adenineMutation rateClinical studiesGenesPreclinical modelsThymine contentDysregulation 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
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
2012
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5803-5808. PMID: 22451909, PMCID: PMC3326463, DOI: 10.1073/pnas.1202922109.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisTDP-43 proteinopathyTDP-43Human neuronsTransactive response DNA binding proteinFrontotemporal lobar degenerationFamilial amyotrophic lateral sclerosisFunctional motor neuronsCell-specific vulnerabilityTDP-43 proteinDNA binding proteinPI3K pathwayCell-autonomous phenotypeMotor neuronsLateral sclerosisStem cell linesPluripotent stem cellsGeneration of iPSCsIdentification of mutationsPluripotent stem cell lineMutant neuronsNeuronsK pathwayElevated levelsDisease mechanisms
2008
Disease-Specific Induced Pluripotent Stem Cells
Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-Specific Induced Pluripotent Stem Cells. Cell 2008, 134: 877-886. PMID: 18691744, PMCID: PMC2633781, DOI: 10.1016/j.cell.2008.07.041.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDown syndromeBecker muscular dystrophyType 1 diabetes mellitusHuntington's diseaseStem cellsPluripotent stem cellsDiabetes mellitusDisease-SpecificLesch-Nyhan syndromeDisease-specific stem cellsDiseased patientsCarrier stateTumor cell linesDiseaseSyndromeMuscular dystrophyAdenosine deaminasePatientsDrug developmentInduced pluripotent stem cellsType IIICell linesDiamond syndromeDisease investigation