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
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 malformations
2016
Dnmt1 regulates the myogenic lineage specification of muscle stem cells
Liu R, Kim KY, Jung YW, Park IH. Dnmt1 regulates the myogenic lineage specification of muscle stem cells. Scientific Reports 2016, 6: 35355. PMID: 27752090, PMCID: PMC5082760, DOI: 10.1038/srep35355.Peer-Reviewed Original ResearchConceptsImportant epigenetic markKnockout mouse approachesDNA methylation patternsMuscle stem cellsDaughter DNA strandsDNMT1 regulationEpigenetic marksLineage specificationCellular identityDNA methylationMethylation patternsDNMT1 depletionMyogenic genesMyogenic differentiationLineage fidelityNegative regulatorGene expressionDNMT1Osteogenic lineageFunctional roleFunctional consequencesMouse approachDNA strandsId-1Stem cells
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 researchCellsRole of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC
Kwon YW, Paek JS, Cho HJ, Lee CS, Lee HJ, Park IH, Roh TY, Kang CM, Yang HM, Park YB, Kim HS. Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC. Biomaterials 2015, 59: 102-115. PMID: 25956855, DOI: 10.1016/j.biomaterials.2015.03.031.Peer-Reviewed Original ResearchConceptsMES cellsSomatic cellsCell extractsProtein extractsGlobal gene expressionES-like cellsMouse iPS cellsPluripotent stem cellsCell-derived proteinsHistone modificationsFull reprogrammingEpigenetic statusDNA methylationZscan4Developmental potencyIPSC derivationGene expressionGenomic DNAIPS cellsAdult fibroblastsKey moleculesStem cellsProteinCellsColonies
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 patientsTransformation of somatic cells into stem cell‐like cells under a stromal niche
Lee ST, Gong SP, Yum KE, Lee EJ, Lee CH, Choi JH, Kim DY, Han H, Kim K, Hysolli E, Ahn JY, Park I, Han JY, Jeong J, Lim JM. Transformation of somatic cells into stem cell‐like cells under a stromal niche. The FASEB Journal 2013, 27: 2644-2656. PMID: 23580613, PMCID: PMC4050423, DOI: 10.1096/fj.12-223065.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AggregationCell DedifferentiationCell FusionCells, CulturedChromosome AberrationsCoculture TechniquesEmbryo, MammalianEmbryonic Stem CellsFemaleFibroblastsGene Expression ProfilingInduced Pluripotent Stem CellsKaryotypingMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBAMice, Inbred ICRMicroscopy, Electron, TransmissionOligonucleotide Array Sequence AnalysisOvarySpecies SpecificityStem Cell NicheStem CellsConceptsEmbryonic stem cellsColony-forming fibroblastsParthenogenetic embryonic stem cellsSomatic cellsGenomic single nucleotide polymorphismsAcquisition of pluripotencySomatic cell plasticityPluripotency gene expressionStem cellsInner cell massStem cell-like cellsCell cycle-related proteinsPluripotent stem cellsSomatic genomeCycle-related proteinsGenomic plasticityCell-like cellsSingle nucleotide polymorphismsCell plasticityESC coloniesGenetic manipulationHeterologous recombinationEmbryonic fibroblastsImprinting patternGene expression
2012
The lesser known story of X chromosome reactivation
Hysolli E, Tanaka Y, Kim K, Jung Y, Park IH. The lesser known story of X chromosome reactivation. Cell Cycle 2012, 11: 229-235. PMID: 22234239, PMCID: PMC3293375, DOI: 10.4161/cc.11.2.18998.Peer-Reviewed Original ResearchConceptsX chromosome reactivationX-chromosome inactivationInner cell massActive histone marksGerm cell formationX inactivation signalHistone marksActive chromosomeCellular reprogrammingInactivation signalGene poolPluripotent cellsKey regulatorFemale cellsGene expressionGerm layersCell formationXY cellsCell massImportant mechanismNatural occurrenceCellsReprogrammingChromosomesGenes
2009
A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells
Lee JH, Park IH, Gao Y, Li JB, Li Z, Daley GQ, Zhang K, Church GM. A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells. PLOS Genetics 2009, 5: e1000718. PMID: 19911041, PMCID: PMC2766639, DOI: 10.1371/journal.pgen.1000718.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell DifferentiationCell LineCells, CulturedCluster AnalysisComputational BiologyDNA, ComplementaryFlow CytometryGene Expression RegulationHuman Genome ProjectHumansInduced Pluripotent Stem CellsNucleic Acid Amplification TechniquesOrgan SpecificityRegulatory Elements, TranscriptionalReproducibility of ResultsConceptsCis-regulatory variantsPluripotent stem cellsRegulatory polymorphismsGene expressionAllele-specific gene expressionIPS cellsPrimary fibroblastsCell typesAllele-specific expressionHigh-throughput sequencingStem cellsHuman iPS cellsSkin primary fibroblastsRegulatory variantsTissue-specific variantsX chromosomeDifferentiated derivativesExpression locusCell differentiationSpecific tissuesLymphoblastoid cellsDigital-RNAPadlock probesExpressionCells
2007
Reprogramming of human somatic cells to pluripotency with defined factors
Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2007, 451: 141-146. PMID: 18157115, DOI: 10.1038/nature06534.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCell DifferentiationCell ShapeCells, CulturedDNA MethylationDNA-Binding ProteinsEmbryonic Stem CellsFetusFibroblastsGene Expression ProfilingHMGB ProteinsHomeodomain ProteinsHumansInfant, NewbornKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsPromoter Regions, GeneticProto-Oncogene Proteins c-mycSOXB1 Transcription FactorsTeratomaTranscription FactorsTransplantation, HeterologousConceptsEmbryonic stem cellsStem cellsIPS cellsHuman somatic cellsInduced pluripotent stem cellsHuman iPS cellsPluripotent stem cellsHuman primary cellsPatient-specific cellsEarly embryosTranscription factorsSomatic cellsEctopic expressionPluripotencyGene expressionHuman cellsMurine fibroblastsDefined factorsPrimary cellsCell linesDermal fibroblastsCellsInvaluable toolFibroblastsExpression