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
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
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 researchCells
2014
Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline
Watanabe T, Cheng EC, Zhong M, Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Research 2014, 25: 368-380. PMID: 25480952, PMCID: PMC4352877, DOI: 10.1101/gr.180802.114.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPiRNA pathwayRetrotransposon sequencesIntergenic regionMammalian PIWI-interacting RNAsRNA regulatory networkLate spermatocytesVivo functional analysisDegradation of mRNAUTR of mRNAsSlicer activityEukaryotic genomesLncRNA transcriptomeRegulatory networksRegulatory sequencesRepetitive sequencesPseudogenesMRNA stabilityFunctional analysisLncRNAsWidespread expressionSpermatid stageRetrotransposonsMRNATransposon
2013
PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells
Juliano CE, Reich A, Liu N, Götzfried J, Zhong M, Uman S, Reenan RA, Wessel GM, Steele RE, Lin H. PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 111: 337-342. PMID: 24367095, PMCID: PMC3890812, DOI: 10.1073/pnas.1320965111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsCell DifferentiationCell LineageCell SeparationCytoplasmEpithelial CellsFlow CytometryGene Expression RegulationHydraPhylogenyRecombinant ProteinsRNARNA InterferenceRNA Processing, Post-TranscriptionalRNA, Small InterferingSpecies SpecificityStem CellsTranscriptomeTransgenesConceptsPIWI-interacting RNAsPIWI proteinsStem/progenitor cellsProgenitor cellsPIWI-piRNA pathwayPing-pong signatureSomatic stem/progenitor cellsStem cell functionalitySomatic stem cellsInterstitial lineageNonbilaterian animalsPiwi functionPiRNA biogenesisAnimal germlineTransposon transcriptsSimple metazoanCnidarian HydraSmall RNAsEndodermal lineagesRNA functionPosttranscriptional regulatorsEpithelial lineageLineagesLikely actsPiwiTranscriptional 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