2024
Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline
Jang Y, Tomasini L, Bae T, Szekely A, Vaccarino F, Abyzov A. Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline. Nature Communications 2024, 15: 9117. PMID: 39438473, PMCID: PMC11496613, DOI: 10.1038/s41467-024-53485-x.Peer-Reviewed Original Research
2023
Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis
Jourdon A, Wu F, Mariani J, Capauto D, Norton S, Tomasini L, Amiri A, Suvakov M, Schreiner J, Jang Y, Panda A, Nguyen C, Cummings E, Han G, Powell K, Szekely A, McPartland J, Pelphrey K, Chawarska K, Ventola P, Abyzov A, Vaccarino F. Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nature Neuroscience 2023, 26: 1505-1515. PMID: 37563294, PMCID: PMC10573709, DOI: 10.1038/s41593-023-01399-0.Peer-Reviewed Original ResearchConceptsIdiopathic autism spectrum disorderCortical neuron subtypesAutism spectrum disorderEarly cortical developmentCortical organoidsCortical plateExcitatory neuronsCortical developmentRare formNeuron subtypesUnaffected fatherASD pathogenesisForebrain organoidsEarly neurogenesisRare variantsIdiopathic autismRisk genesTranscriptomic alterationsNeuronsProbandsSingle-cell transcriptomicsForebrain developmentSpectrum disorderTranscriptomic changesAlterationsEfficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang Y, Fasching L, Bae T, Tomasini L, Schreiner J, Szekely A, Fernandez T, Leckman J, Vaccarino F, Abyzov A. Efficient reconstruction of cell lineage trees for cell ancestry and cancer. Nucleic Acids Research 2023, 51: e57-e57. PMID: 37026484, PMCID: PMC10250207, DOI: 10.1093/nar/gkad254.Peer-Reviewed Original ResearchConceptsLineage treesCell ancestryCell lineage treesFirst cell divisionStem cell linesPluripotent stem cell lineLineage reconstructionInduced pluripotent stem cell lineCell divisionCancer progressionLineage representationCell linesMosaic mutationsHuman skin fibroblastsTreesMutationsAncestrySkin fibroblastsMultiple cellsGenomeLineagesZygotesLinesFibroblastsCells
2022
Characterization of human basal ganglia organoids
Brady M, Mariani J, Koca Y, Szekely A, King R, Bloch M, Landeros-Weisenberger A, Leckman J, Vaccarino F. Characterization of human basal ganglia organoids. Molecular Psychiatry 2022, 27: 4823-4823. PMID: 36536052, DOI: 10.1038/s41380-022-01914-y.Peer-Reviewed Original ResearchMispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids
Brady M, Mariani J, Koca Y, Szekely A, King R, Bloch M, Landeros-Weisenberger A, Leckman J, Vaccarino F. Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids. Molecular Psychiatry 2022, 27: 5007-5019. PMID: 36447010, PMCID: PMC9949887, DOI: 10.1038/s41380-022-01880-5.Peer-Reviewed Original ResearchConceptsTourette syndromeInterneuron deficitsGABAergic interneuronsHealthy controlsNeurodevelopmental underpinningsNeuropathological deficitsBG circuitryNeuropsychiatric disordersDecreased differentiationT patientsInterneuronsAltered expressionPotential mechanismsCilia disruptionSonic hedgehogOrganoidsStem cellsTS individualsPluripotent stem cellsGli transcription factorsDeficitsOrganoid differentiationEarly stagesCholinergicPatients
2021
Early developmental asymmetries in cell lineage trees in living individuals
Fasching L, Jang Y, Tomasi S, Schreiner J, Tomasini L, Brady MV, Bae T, Sarangi V, Vasmatzis N, Wang Y, Szekely A, Fernandez TV, Leckman JF, Abyzov A, Vaccarino FM. Early developmental asymmetries in cell lineage trees in living individuals. Science 2021, 371: 1245-1248. PMID: 33737484, PMCID: PMC8324008, DOI: 10.1126/science.abe0981.Peer-Reviewed Original Research
2020
Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9
Chai H, Ji W, Wen J, DiAdamo A, Grommisch B, Hu Q, Szekely AM, Li P. Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9. American Journal Of Medical Genetics Part A 2020, 182: 3023-3028. PMID: 32978894, DOI: 10.1002/ajmg.a.61890.Peer-Reviewed Original Research
2016
Effective Treatment of Paroxysmal Nonkinesigenic Dyskinesia With Oxcarbazepine
Kumar A, Szekely A, Jabbari B. Effective Treatment of Paroxysmal Nonkinesigenic Dyskinesia With Oxcarbazepine. Clinical Neuropharmacology 2016, 39: 201-205. PMID: 27046658, DOI: 10.1097/wnf.0000000000000149.Peer-Reviewed Original ResearchConceptsParoxysmal nonkinesigenic dyskinesiaRare chronic disorderOutcome of treatmentSeverity of episodesAvailable therapiesChronic disordersClinical trialsInvoluntary movementsEffective treatmentOxcarbazepinePharmaceutical agentsDyskinesiaPatientsTreatmentDisordersTherapyDebilitatingDiseaseTrialsSeverity
2015
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, Amenduni M, Szekely A, Palejev D, Wilson M, Gerstein M, Grigorenko EL, Chawarska K, Pelphrey KA, Howe JR, Vaccarino FM. FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders. Cell 2015, 162: 375-390. PMID: 26186191, PMCID: PMC4519016, DOI: 10.1016/j.cell.2015.06.034.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsGene network analysisGene network modulesUpregulation of genesTranscription factor Foxg1Accelerated cell cyclePluripotent stem cellsRNA interferenceGenetic basisSynaptic assemblyCell cycleBrain developmentNeuron fateNeuron differentiationNeuronal differentiationGenomic mutationsHuman brain developmentIdiopathic autism spectrum disorderAltered expressionStem cellsCell proliferationFOXG1ASD pathophysiologyNetwork modulesNeural cultures
2013
Primary dystonias and genetic disorders with dystonia as clinical feature of the disease
Moghimi N, Jabbari B, Szekely AM. Primary dystonias and genetic disorders with dystonia as clinical feature of the disease. European Journal Of Paediatric Neurology 2013, 18: 79-105. PMID: 23911094, DOI: 10.1016/j.ejpn.2013.05.015.Peer-Reviewed Original ResearchConceptsPrimary dystoniaClinical featuresSustained muscle contractionsCharacteristic clinical featuresClinical entityAbnormal postureMovement disordersDystoniaClinical practiceClinical phenomenologyAdvances of geneticsGenetic syndromesMuscle contractionRepetitive movementsUnderlining etiologiesDisordersCommon formMonogenic disordersGenetic disordersMolecular underpinningsDetailed searchMendelian disordersComplex casesLarge groupSyndromeFunctional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration
Zhang Y, Schulz VP, Reed BD, Wang Z, Pan X, Mariani J, Euskirchen G, Snyder MP, Vaccarino FM, Ivanova N, Weissman SM, Szekely AM. Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12361-12366. PMID: 23836664, PMCID: PMC3725080, DOI: 10.1073/pnas.1309725110.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsFunctional genomic screensGenomic screenUndifferentiated human embryonic stem cellsNeural lineage developmentSet of genesHuman stem cell differentiationProgenitor cell formationEmbryonic stem cellsStem cell differentiationRNA library screenNeuronal progenitor cellsLate-onset neurodegenerative disorderUnpredicted genesRNA granulesNext-generation sequencingSelf-renewal capacityLineage developmentComplex inheritanceShRNA libraryEarly neurogenesisLibrary screenParallel sequencingCell differentiationGenes
2012
Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells
Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS, Tomasini L, Ferrandino AF, Rosenberg Belmaker LA, Szekely A, Wilson M, Kocabas A, Calixto NE, Grigorenko EL, Huttner A, Chawarska K, Weissman S, Urban AE, Gerstein M, Vaccarino FM. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 2012, 492: 438-442. PMID: 23160490, PMCID: PMC3532053, DOI: 10.1038/nature11629.Peer-Reviewed Original ResearchA highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells
Charos AE, Reed BD, Raha D, Szekely AM, Weissman SM, Snyder M. A highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells. Genome Research 2012, 22: 1668-1679. PMID: 22955979, PMCID: PMC3431484, DOI: 10.1101/gr.127761.111.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCarrier ProteinsChromatin ImmunoprecipitationCluster AnalysisGene Expression RegulationGene Regulatory NetworksHeat-Shock ProteinsHep G2 CellsHigh-Throughput Nucleotide SequencingHumansNucleotide MotifsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaProtein BindingProtein TransportTranscription FactorsTranscription, GeneticConceptsTranscription factorsGenome-wide binding sitesCombinatorial binding patternsHeat shock response pathwayIndividual transcription factorsTranscriptional regulatory networksDNA sequence motifsDifferent transcription factorsShock response pathwayHigh-throughput sequencingMetabolic gene expressionHepG2 cellsTF partnersTranscriptional dynamicsCellular processesChIP-seqSequence motifsRegulatory networksTranscriptional coactivatorResponse pathwaysInterdependent regulationTarget genesChromatin IPRegulatory codeGene expressionModeling human cortical development in vitro using induced pluripotent stem cells
Mariani J, Simonini MV, Palejev D, Tomasini L, Coppola G, Szekely AM, Horvath TL, Vaccarino FM. Modeling human cortical development in vitro using induced pluripotent stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12770-12775. PMID: 22761314, PMCID: PMC3411972, DOI: 10.1073/pnas.1202944109.Peer-Reviewed Original ResearchConceptsHuman brain developmentHuman induced pluripotent stem cellsLayer-specific cortical neuronsBrain developmentHuman cerebral cortexHuman cortical developmentStem cellsPluripotent stem cellsCerebral cortexCortical neuronsCortical developmentCNS regionsRadial gliaCortical wallDorsal telencephalonEmbryonic telencephalonGene expression profilesInduced pluripotent stem cellsIntermediate progenitorsTelencephalic developmentTelencephalonExpression profilesTranscriptional programsCellsGlia
2011
Induced pluripotent stem cells: A new tool to confront the challenge of neuropsychiatric disorders
Vaccarino FM, Stevens HE, Kocabas A, Palejev D, Szekely A, Grigorenko EL, Weissman S. Induced pluripotent stem cells: A new tool to confront the challenge of neuropsychiatric disorders. Neuropharmacology 2011, 60: 1355-1363. PMID: 21371482, PMCID: PMC3087494, DOI: 10.1016/j.neuropharm.2011.02.021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInduced pluripotent stem cellsUse of iPSCsPluripotent stem cellsStem cellsEmbryonic stem cellsEarly developmental eventsMature somatic cellsEarly developmental stagesSomatic cellsGenetic variationGene productsDevelopmental eventsReprogramming strategiesNeural differentiationHuman brain developmentDevelopmental stagesIPSC technologyNeurodevelopmental pathwaysDevelopmental originsGenesPotential pharmacological interventionsNew toolGenetic deficitsCellsNeuropsychiatric disordersAnnual Research Review: The promise of stem cell research for neuropsychiatric disorders
Vaccarino FM, Urban AE, Stevens HE, Szekely A, Abyzov A, Grigorenko EL, Gerstein M, Weissman S. Annual Research Review: The promise of stem cell research for neuropsychiatric disorders. Journal Of Child Psychology And Psychiatry 2011, 52: 504-516. PMID: 21204834, PMCID: PMC3124336, DOI: 10.1111/j.1469-7610.2010.02348.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNervous systemNeuropsychiatric disordersPsychiatric disordersAdult-onset neuropsychiatric disordersEarly onset neuropsychiatric disordersHuman neural cellsAttention deficit hyperactivity disorderStem cellsNeural stem cellsDeficit hyperactivity disorderHuman brain developmentObsessive-compulsive disorderPharmacological interventionsFunctional neuronsBrain developmentUse of iPSCsNeural cellsHyperactivity disorderTime pointsDisordersCompulsive disorderPatientsNeural differentiationDevelopmental time pointsNeurodevelopmental conditions
2010
Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing
Wu JQ, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman S, Cui W, Gerstein M, Snyder M. Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 5254-5259. PMID: 20194744, PMCID: PMC2841935, DOI: 10.1073/pnas.0914114107.Peer-Reviewed Original ResearchConceptsNeural differentiationUndifferentiated hESCsNeural fate specificationCell identity maintenanceStage-specific regulationHuman embryonic stem cellsTypes of genesPaired-end sequencingDifferentiation of hESCsEmbryonic stem cellsPaired-end readsNeural cell differentiationSplicing dynamicsFate specificationDynamic transcriptomeIsoform diversityTranscriptome changesUnannotated transcriptsGene transcriptionRNA sequencingStages of differentiationNeural lineagesCell differentiationDifferential expressionGliogenic potential
2008
Genome-Wide Occupancy of SREBP1 and Its Partners NFY and SP1 Reveals Novel Functional Roles and Combinatorial Regulation of Distinct Classes of Genes
Reed BD, Charos AE, Szekely AM, Weissman SM, Snyder M. Genome-Wide Occupancy of SREBP1 and Its Partners NFY and SP1 Reveals Novel Functional Roles and Combinatorial Regulation of Distinct Classes of Genes. PLOS Genetics 2008, 4: e1000133. PMID: 18654640, PMCID: PMC2478640, DOI: 10.1371/journal.pgen.1000133.Peer-Reviewed Original ResearchConceptsTarget genesGenome-wide occupancyDNA-binding motifComplex transcriptional responseGenome tiling arraysDiverse biological pathwaysSREBP1 target genesCritical transcriptional regulatorNovel functional roleGene expression microarraysDistinct functional pathwaysCombinatorial regulationTarget promotersTranscriptional regulatorsTiling arraysRegulatory circuitryTranscriptional responseChromatin immunoprecipitationFatty acid metabolismExpression microarraysFunctional pathwaysBiological pathwaysHepatocyte cell lineHuman hepatocyte cell lineSp1
2006
Karyotype–phenotype insights from 11q14.1‐q23.2 interstitial deletions: FZD4 haploinsufficiency and exudative vitreoretinopathy in a patient with a complex chromosome rearrangement
Li P, Zhang HZ, Huff S, Nimmakayalu M, Qumsiyeh M, Yu J, Szekely A, Xu T, Pober BR. Karyotype–phenotype insights from 11q14.1‐q23.2 interstitial deletions: FZD4 haploinsufficiency and exudative vitreoretinopathy in a patient with a complex chromosome rearrangement. American Journal Of Medical Genetics Part A 2006, 140A: 2721-2729. PMID: 17103440, DOI: 10.1002/ajmg.a.31498.Peer-Reviewed Original ResearchAbnormalities, MultipleBase SequenceChild, PreschoolChromosome DeletionChromosomes, Human, Pair 11Cleft PalateCraniofacial AbnormalitiesDNA PrimersExudates and TransudatesFemaleFingersFrizzled ReceptorsHumansKaryotypingModels, GeneticPhenotypeReceptors, G-Protein-CoupledRetinal DiseasesToesVitreous Body
2005
Werner Protein Protects Nonproliferating Cells from Oxidative DNA Damage
Szekely AM, Bleichert F, Nümann A, Van Komen S, Manasanch E, Nasr A, Canaan A, Weissman SM. Werner Protein Protects Nonproliferating Cells from Oxidative DNA Damage. Molecular And Cellular Biology 2005, 25: 10492-10506. PMID: 16287861, PMCID: PMC1291253, DOI: 10.1128/mcb.25.23.10492-10506.2005.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesCell ProliferationCells, CulturedCellular SenescenceDNADNA DamageDNA HelicasesDNA ReplicationExodeoxyribonucleasesFibroblastsGene Expression RegulationHumansOxidation-ReductionOxidative StressOxygenRecQ HelicasesRNA InterferenceTelomeric Repeat Binding Protein 2Werner Syndrome HelicaseConceptsDNA damage responseWerner syndromeDamage responseDNA damageRNA interferenceOxidative DNA damageWRN-depleted cellsInduction of gammaH2AXDNA damage fociCellular senescence phenotypePrimary human fibroblastsWRN depletionWerner proteinWRN proteinNuclear fociWRN deficiencyProtein TRF2Telomere maintenanceAcute oxidative stressBLM expressionDNA homeostasisDNA replicationDamage fociSenescence phenotypePhysiological oxygen