2023
High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
Mendes H, Neelakantan U, Liu Y, Fitzpatrick S, Chen T, Wu W, Pruitt A, Jin D, Jamadagni P, Carlson M, Lacadie C, Enriquez K, Li N, Zhao D, Ijaz S, Sakai C, Szi C, Rooney B, Ghosh M, Nwabudike I, Gorodezky A, Chowdhury S, Zaheer M, McLaughlin S, Fernandez J, Wu J, Eilbott J, Vander Wyk B, Rihel J, Papademetris X, Wang Z, Hoffman E. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Reports 2023, 42: 112243. PMID: 36933215, PMCID: PMC10277173, DOI: 10.1016/j.celrep.2023.112243.Peer-Reviewed Original ResearchConceptsGene lossFunctional analysisHigh-throughput functional analysisZebrafish mutantsGene discoverySelect mutantsASD genesAutism genesKey pathwaysASD biologyBrain size differencesMutantsGenesSize differencesPathwayGlobal increaseRelevant mechanismsBiologyCentral challengeNeuroimmune dysfunctionRegionFunctionDiscoveryAutism spectrum disorder
2021
Multi-omics analysis to identify susceptibility genes for colorectal cancer
Yuan Y, Bao J, Chen Z, Villanueva A, Wen W, Wang F, Zhao D, Fu X, Cai Q, Long J, Shu X, Zheng D, Moreno V, Zheng W, Lin W, Guo X. Multi-omics analysis to identify susceptibility genes for colorectal cancer. Human Molecular Genetics 2021, 30: 321-330. PMID: 33481017, PMCID: PMC8485221, DOI: 10.1093/hmg/ddab021.Peer-Reviewed Original ResearchMeSH KeywordsCarcinogenesisCell Line, TumorCell ProliferationColorectal NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGenetic Association StudiesGenetic Predisposition to DiseaseGenomeGenome-Wide Association StudyHumansNerve Tissue ProteinsPolymorphism, Single NucleotideRepressor ProteinsRisk FactorsTranscriptomeConceptsGenome-wide association studiesMulti-omics analysisSusceptibility genesTarget genesPutative target genesGWAS-identified variantsMost genetic variantsDNA methylation dataNovel susceptibility genesGenotype-Tissue ExpressionGenetic risk lociPutative susceptibility genesGene regulationIntergenic regionPathogenic dysregulationCancer Genome AtlasEpithelial-mesenchymal transitionRisk lociGene expressionMethylation dataAssociation studiesGenesCell behaviorGenetic variantsGenome Atlas
2020
Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation
Ryu HY, Zhao D, Li J, Su D, Hochstrasser M. Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation. Nucleic Acids Research 2020, 48: gkaa1093-. PMID: 33231641, PMCID: PMC7708062, DOI: 10.1093/nar/gkaa1093.Peer-Reviewed Original ResearchConceptsHistone deacetylase complexSet3 histone deacetylase complexHistone sumoylationTrans-tail regulationGenome-wide analysisSUMO-interacting motifSUMO conjugation pathwayAltered gene expression profilesDeacetylation of histonesGene expression profilesSet3 complexH2B ubiquitylationDeacetylase complexSpurious transcriptionRNA genesTranscriptional regulationActive genesTranscriptional fidelityTranscription initiationSUMOylationMRNA genesExpression profilesCrosstalk pathwaysHistone deacetylaseGenes
2018
PRC1 preserves epidermal tissue integrity independently of PRC2
Cohen I, Zhao D, Menon G, Nakayama M, Koseki H, Zheng D, Ezhkova E. PRC1 preserves epidermal tissue integrity independently of PRC2. Genes & Development 2018, 33: 55-60. PMID: 30567998, PMCID: PMC6317312, DOI: 10.1101/gad.319939.118.Peer-Reviewed Original ResearchConceptsAdhesion genesEpidermal tissue integrityLoss of PRC1PRC1 functionChromatin regulatorsEpigenetic regulationMolecular dissectionPRC2PRC1Gene expressionTissue developmentSkin morphogenesisFunctional linkSkin fragility syndromeEpidermal stratificationEpidermal integrityTissue integrityGenesExpressionH3K27me3Fragility syndromeMorphogenesisRegulatorCobindingRegulationPRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification
Cohen I, Zhao D, Bar C, Valdes VJ, Dauber-Decker KL, Nguyen MB, Nakayama M, Rendl M, Bickmore WA, Koseki H, Zheng D, Ezhkova E. PRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification. Cell Stem Cell 2018, 22: 726-739.e7. PMID: 29727681, PMCID: PMC5944606, DOI: 10.1016/j.stem.2018.04.005.Peer-Reviewed Original ResearchConceptsNon-canonical PRC1 complexesStem cell specificationPRC1 complexesCell specificationSkin developmentDiverse rolesRepressive Complex 1Essential chromatin regulatorsPrecise developmental programExpression of genesCanonical PRC1PRC1 bindsPRC1 functionChromatin regulatorsGene repressionActive genesCell identityRepressor functionDevelopmental programSC formationFurther dissectionGenesPRC2PRC1Function studiesEnriched expression of genes associated with autism spectrum disorders in human inhibitory neurons
Wang P, Zhao D, Lachman HM, Zheng D. Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons. Translational Psychiatry 2018, 8: 13. PMID: 29317598, PMCID: PMC5802446, DOI: 10.1038/s41398-017-0058-6.Peer-Reviewed Original ResearchConceptsASD candidatesEnriched expressionSingle-cell transcriptomic dataSingle-cell transcriptome profilesCo-expression gene modulesDifferent developmental stagesExcitatory/inhibitory (E/I) imbalance hypothesisInhibitory neuronsGene networksTranscriptome profilesGene modulesTranscriptomic dataUpregulated genesDownstream targetsGene expressionDevelopmental stagesCell typesGenesNeuron subtypesFunctional evidenceAutism spectrum disorderExpressionASD brainCortex samplesExcitatory neurons
2017
Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis
Zhao D, Lin M, Pedrosa E, Lachman HM, Zheng D. Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis. BMC Genomics 2017, 18: 860. PMID: 29126398, PMCID: PMC5681780, DOI: 10.1186/s12864-017-4261-x.Peer-Reviewed Original ResearchConceptsMonoallelic expressionHuman brain cellsGene expressionMonoallelic gene expressionAllelic gene expressionGenome-wide levelSingle-cell RNA-seq datasetsRNA-seq data analysisAllelic expression studiesSingle-cell RNA-seq data analysisRNA-seq datasetsSingle nucleotide variantsBrain cellsCellular identityAutosomal genesNeuronal diversityExpression studiesNucleotide variantsCorrelated expressionGenesIndividual cellsHuman psychiatric disordersNeuronal cellsSingle cellsCell functionTranscriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress
Zhao D, Mokhtari R, Pedrosa E, Birnbaum R, Zheng D, Lachman HM. Transcriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress. Molecular Autism 2017, 8: 17. PMID: 28367307, PMCID: PMC5372344, DOI: 10.1186/s13229-017-0134-z.Peer-Reviewed Original ResearchConceptsHeat shock protein familyShock protein familyWhole transcriptome analysisChromatin regulatorsAnalysis of microgliaPhenotypic phasesTranscriptome analysisProtein familyRNA-seqCellular stressMethyl-CpGRTT phenotypeRTT pathogenesisDe novo lossGene expressionM2 activation statesFemale miceDifferential expressionFunction mutationsHSP pathwayGenesMolecular pathwaysCell typesExtracellular matrixProtein 2
2016
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks
Nebel RA, Zhao D, Pedrosa E, Kirschen J, Lachman HM, Zheng D, Abrahams BS. Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PLOS ONE 2016, 11: e0148039. PMID: 26824476, PMCID: PMC4732616, DOI: 10.1371/journal.pone.0148039.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBase SequenceChromosomes, Human, Pair 15EpilepsyGene Expression ProfilingGene Expression RegulationGene Knockdown TechniquesGene Regulatory NetworksGenetic LociHeterozygoteHumansMaleMiddle AgedMolecular Sequence DataNerve Tissue ProteinsNeural Stem CellsPrimary Cell CultureRiskSchizophreniaSequence DeletionConceptsEpilepsy genesRole of CYFIP1Novel disease candidatesHuman neural progenitorsEpilepsy riskSubset of DEGsPostsynaptic density genesNeuronal differentiationFMRP targetsGene networksNeural progenitorsSchizophreniaCytoskeletal remodelingRNA-seqDeletion carriersKnockdown experimentsVariable expressivityDisease genesProgenitors resultsDisease candidatesGenesCellular assaysCYFIP1DisordersDysregulationDivergence and rewiring of regulatory networks for neural development between human and other species
Wang P, Zhao D, Rockowitz S, Zheng D. Divergence and rewiring of regulatory networks for neural development between human and other species. Neurogenesis 2016, 3: e1231495. PMID: 27900343, PMCID: PMC5111580, DOI: 10.1080/23262133.2016.1231495.Peer-Reviewed Original ResearchRegulatory networksTranscription factorsNeural developmentMouse embryonic stem cellsREST-binding sitesGene regulatory networksCritical transcriptional regulatorREST/NRSFEmbryonic stem cellsTranscriptional regulatorsEpigenetic regulationGenomic regionsGenetic controlMammalian speciesFunctional implicationsGenesStem cellsRest regulationsSpeciesBinding eventsFunctional featuresCritical roleRegulationBrain developmentRecent analysis
2015
MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del
Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, Zheng D, Lachman HM. MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del. PLOS ONE 2015, 10: e0132387. PMID: 26173148, PMCID: PMC4501820, DOI: 10.1371/journal.pone.0132387.Peer-Reviewed Original ResearchConceptsGenome-wide significanceUnderlying genetic basisInduced pluripotent stem cellsPluripotent stem cell (iPSC) technologyMiRNA expression profilingPluripotent stem cellsMiRNA expression patternsMicroRNA biogenesisMRNA targetsRegulated miRNAsGenetic basisExpression profilingStem cell technologyExpression patternsAutopsy samplesMiRNAsNeuropsychiatric disordersMicroRNA profilingStem cellsNominal significanceGenesPeripheral cellsPeripheral bloodWider significanceGenetic factors
2014
Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon
Lin M, Zhao D, Hrabovsky A, Pedrosa E, Zheng D, Lachman HM. Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon. PLOS ONE 2014, 9: e94968. PMID: 24736721, PMCID: PMC3988108, DOI: 10.1371/journal.pone.0094968.Peer-Reviewed Original ResearchConceptsCopy number variantsCandidate genesHS-inducible genesMaternal immune activationPluripotent stem cell modelsCellular stress pathwaysInduced Pluripotent Stem Cell ModelDisease-causing genetic variantsHeritable neuropsychiatric disorderStem cell modelAutism candidate genesPluripotent stem cellsCommon environmental stressorsCellular stressorsGenes decreasesRNA-seqASD candidatesASD genesHeat shockCopy lossHuman brain developmentEnvironmental stressorsHeat shock altersGenesStress pathways
2013
Efficient utilization of aerobic metabolism helps Tibetan locusts conquer hypoxia
Zhao D, Zhang Z, Cease A, Harrison J, Kang L. Efficient utilization of aerobic metabolism helps Tibetan locusts conquer hypoxia. BMC Genomics 2013, 14: 631. PMID: 24047108, PMCID: PMC3852963, DOI: 10.1186/1471-2164-14-631.Peer-Reviewed Original ResearchConceptsAerobic metabolismBasic metabolic processesExtreme hypoxiaTranscriptional responseHigh-altitude Tibetan PlateauGeographical populationsTCA cycleMigratory locustHypoxia toleranceMetabolic processesLocusta migratoriaHypoxic responseEntry genesLocustPhysiological perspectiveATP contentMetabolismTibetan PlateauInvertebratesInsectsDifferent altitudesGenesSpeciesHypoxiaConclusionsOur results
2012
Identification of condition‐specific reference genes from microarray data for locusts exposed to hypobaric hypoxia
Zhao DJ, Guo K, Kang L. Identification of condition‐specific reference genes from microarray data for locusts exposed to hypobaric hypoxia. FEBS Open Bio 2012, 2: 235-240. PMID: 23650605, PMCID: PMC3642161, DOI: 10.1016/j.fob.2012.08.001.Peer-Reviewed Original ResearchGene expression stabilityReference genesHousekeeping genesExpression stabilityGene expressionNovel candidate reference genesMicroarray dataQuantitative polymerase chain reactionLarge-scale gene expression dataClassical housekeeping genesCandidate reference genesReliable reference genesGene expression dataGenes 18STranscriptional responseStable genesExpression dataGenesΒ-actinReal-time quantitative polymerase chain reactionLocust muscleGeNormNormFinderExpressionPolymerase chain reaction