2024
Characterization and functional analysis of extrachromosomal circular DNA discovered from circulating extracellular vesicles in liver failure
Qian Y, Hong X, Yu Y, Du C, Li J, Yu J, Xiao W, Chen C, Huang D, Zhong T, Li J, Xiang X, Li Z. Characterization and functional analysis of extrachromosomal circular DNA discovered from circulating extracellular vesicles in liver failure. Clinical And Translational Medicine 2024, 14: e70059. PMID: 39406484, PMCID: PMC11479749, DOI: 10.1002/ctm2.70059.Peer-Reviewed Original ResearchWhole-genome Sequencing Association Analysis of Quantitative Platelet Traits in A Large Cohort of β-thalassemia
Wang X, Zhang Q, Chen X, Huang Y, Zhang W, Liao L, Zhang X, Huang B, Huang Y, Ye Y, Song M, Lao J, Chen J, Feng X, Long X, Liu Z, Zhu W, Yu L, Fan C, Tang D, Zhong T, Fang M, Li C, Niu C, Huang L, Lin B, Hua X, Jin X, Li Z, Xu X. Whole-genome Sequencing Association Analysis of Quantitative Platelet Traits in A Large Cohort of β-thalassemia. Genomics Proteomics & Bioinformatics 2024, qzae065. PMID: 39331630, DOI: 10.1093/gpbjnl/qzae065.Peer-Reviewed Original ResearchPlatelet traitsAnalysis of whole-genome sequencing dataWhole-genome sequencing dataFunctional annotation dataGenotype-phenotype association studiesRare variantsLack of genetic studiesMean platelet volumeNoncoding genomeWhole genomeSequence dataAssociation studiesMultiple genesGenetic studiesB-thalassemia patientsB-thalassemiaPhenotypic heterogeneityIntegrated analysisTraitsMissenseGenesPotential targetVariantsRV analysisGenome
2023
Generation 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 developmentPTCHD1NucleusKinaseGenesSequencing
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
2021
Genome-wide mapping of Piwi association with specific loci in Drosophila ovaries
Liu N, Neuenkirchen N, Zhong M, Lin H. Genome-wide mapping of Piwi association with specific loci in Drosophila ovaries. G3: Genes, Genomes, Genetics 2021, 11: jkaa059. PMID: 33609367, PMCID: PMC8022938, DOI: 10.1093/g3journal/jkaa059.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsProtein-coding genesDrosophila ovaryGermline stem cell maintenanceRole of piRNAsTermination sitesGenome-wide mappingGenomic binding profileTranscriptional termination sitesSpecific genomic sitesStem cell maintenanceRNA pathwaysTransposon repressionTranscriptional startEuchromatic regionsGene regulationEpigenetic regulationGenomic sitesCell maintenancePiwiSpecific lociMethylation signalsDiverse mechanismsTarget siteBinding sitesThe Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis
Cheng EC, Hsieh CL, Liu N, Wang J, Zhong M, Chen T, Li E, Lin H. The Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis. Cell Reports 2021, 34: 108575. PMID: 33406415, PMCID: PMC8513770, DOI: 10.1016/j.celrep.2020.108575.Peer-Reviewed Original ResearchConceptsEarly meiosisEarly meiotic prophase IFunction of SETDB1Homologous chromosome pairingMeiotic prophase IHistone-lysine N-methyltransferaseMeiotic silencingSurvival of spermatocytesGermline developmentBouquet formationHomologous chromosomesLineage genesChromosome pairingBivalent formationPericentromeric regionProphase IApoptosis of spermatocytesSETDB1Essential functionsHomologous bivalentsH3K9me3Meiotic arrestMeiosisSpermatocytesN-methyltransferase
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 driverPublisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors
Chen X, Burkhardt DB, Hartman AA, Hu X, Eastman AE, Sun C, Wang X, Zhong M, Krishnaswamy S, Guo S. Publisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors. Nature Communications 2020, 11: 681. PMID: 31996673, PMCID: PMC6989496, DOI: 10.1038/s41467-020-14428-4.Peer-Reviewed Original Research
2019
MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors
Chen X, Burkhardt DB, Hartman AA, Hu X, Eastman AE, Sun C, Wang X, Zhong M, Krishnaswamy S, Guo S. MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors. Nature Communications 2019, 10: 5767. PMID: 31852898, PMCID: PMC6920141, DOI: 10.1038/s41467-019-13666-5.Peer-Reviewed Original ResearchAnimalsCell CycleCell DifferentiationCell ProliferationCell Transformation, NeoplasticCyclin D1Disease Models, AnimalFemaleGene Expression Regulation, LeukemicGene Knock-In TechniquesHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMice, TransgenicMyeloid Progenitor CellsMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPiperazinesPrimary Cell CulturePrognosisPyridinesEngineering 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 ResearchConceptsHuman 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 deliveryCellsEndotheliumMicrovasculatureMKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpressionhESC-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
2018
Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a
Kim KY, Tanaka Y, Su J, Cakir B, Xiang Y, Patterson B, Ding J, Jung YW, Kim JH, Hysolli E, Lee H, Dajani R, Kim J, Zhong M, Lee JH, Skalnik D, Lim JM, Sullivan GJ, Wang J, Park IH. Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nature Communications 2018, 9: 2583. PMID: 29968706, PMCID: PMC6030064, DOI: 10.1038/s41467-018-04818-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCAAT-Enhancer-Binding ProteinsCellular ReprogrammingCellular Reprogramming TechniquesChimeraDNA MethylationEpigenesis, GeneticFemaleFibroblastsGene Knockout TechniquesHEK293 CellsHistone CodeHistone-Lysine N-MethyltransferaseHistonesHumansMaleMesodermMiceMouse Embryonic Stem CellsNeural PlateNuclear ProteinsPrimary Cell CultureRecombinant ProteinsUbiquitin-Protein LigasesConceptsEmbryonic stem cellsUnique epigenetic statesBivalent histone modificationsRecruitment of DNMT1Bivalent histone marksCell typesDNA-binding proteinsSpecialized cell typesStem cellsPluripotent stem cellsTrithorax groupBivalent domainsMesoderm specificationCOMPASS complexHeterochromatin formationEpigenetic stateCell specificationHistone marksLineage specificationHistone modificationsEpigenetic regulationSpecific lineagesDNA methylationTranscriptional marksEpigenetic changes
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
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 ResearchConceptsDNA 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 analysisReprogrammingDNA methylation on N6-adenine in mammalian embryonic stem cells
Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ. DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 2016, 532: 329-333. PMID: 27027282, PMCID: PMC4977844, DOI: 10.1038/nature17640.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlkB Homolog 1, Histone H2a DioxygenaseAnimalsCell DifferentiationDNA MethylationDNA Transposable ElementsDNA-(Apurinic or Apyrimidinic Site) LyaseEnhancer Elements, GeneticEpigenesis, GeneticEvolution, MolecularGene SilencingLong Interspersed Nucleotide ElementsMammalsMiceMouse Embryonic Stem CellsUp-RegulationX ChromosomeConceptsLINE-1 transposonsEmbryonic stem cellsN6-methyladenineMammalian genomesEpigenetic silencingDNA methylationX chromosomeMammalian embryonic stem cellsEmbryonic stem cell differentiationMouse embryonic stem cellsStem cellsStem cell differentiationMammalian evolutionTranscriptional silencingEvolutionary ageGene activationDNA modificationsL1 elementsCell differentiationSilencingTransposonN6-adenineGenomeActivation signalsChromosomes
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 researchCellsTranscriptional 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 signatureReassessment of Piwi Binding to the Genome and Piwi Impact on RNA Polymerase II Distribution
Lin H, Chen M, Kundaje A, Valouev A, Yin H, Liu N, Neuenkirchen N, Zhong M, Snyder M. Reassessment of Piwi Binding to the Genome and Piwi Impact on RNA Polymerase II Distribution. Developmental Cell 2015, 32: 772-774. PMID: 25805139, PMCID: PMC4472434, DOI: 10.1016/j.devcel.2015.03.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsBase SequenceBinding SitesChromatin ImmunoprecipitationChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDrosophila melanogasterDrosophila ProteinsGenomeHigh-Throughput Nucleotide SequencingHistone MethyltransferasesHistone-Lysine N-MethyltransferaseMethyltransferasesRNA InterferenceRNA Polymerase IIRNA, Small InterferingSequence Analysis, DNAConceptsRNA polymerase II distributionGenomic targetsHeterochromatin protein 1aRNA polymerase IICurrent bioinformatics methodsPiwi mutantsDrosophila PiwiPolymerase IIDevelopmental cellsPericentric regionsHistone methyltransferaseBioinformatics methodsBioinformatics pipelineProtein 1APiwiGenomePiRNAsEuchromatinMutantsMethyltransferaseSitesCharacterization of the mammalian miRNA turnover landscape
Guo Y, Liu J, Elfenbein SJ, Ma Y, Zhong M, Qiu C, Ding Y, Lu J. Characterization of the mammalian miRNA turnover landscape. Nucleic Acids Research 2015, 43: 2326-2341. PMID: 25653157, PMCID: PMC4344502, DOI: 10.1093/nar/gkv057.Peer-Reviewed Original ResearchConceptsMiRNA turnoverStable small RNAsMammalian cell typesCultured mammalian cellsSubset of miRNAsTurnover kineticsMiRNA biogenesisMost miRNAsMiR-222-5pNucleotide biasSmall RNAsMiRNA maturationMammalian cellsSame miRNAMiRNA poolExpression profilingHsp90 associationSequence determinantsDeep sequencingHsp90 inhibitionTurnover rateMiRNA isoformsDifferent turnover ratesSequence featuresCell types