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
Maternal FGF2 levels associated with child anxiety and depression symptoms through child FGF2 levels
Lebowitz E, Marin C, Orbach M, Salmaso N, Vaccarino F, Silverman W. Maternal FGF2 levels associated with child anxiety and depression symptoms through child FGF2 levels. Journal Of Affective Disorders 2023, 326: 193-197. PMID: 36717031, PMCID: PMC10104478, DOI: 10.1016/j.jad.2023.01.090.Peer-Reviewed Original ResearchConceptsFGF2 levelsDepressive symptomsDepression symptomsChild anxietySymptoms of anxietyRatings of anxietyGrowth factor 2Maternal anxietySymptomsDepressed childrenDepressionChild depressionMothersChildrenFactor 2Self-report ratingsAnxietyIntergenerational pathwaysNon-referred childrenRange of anxietyFGF2AssociationLevelsMaternal
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 ResearchMachine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia
Zhu X, Zhou B, Pattni R, Gleason K, Tan C, Kalinowski A, Sloan S, Fiston-Lavier AS, Mariani J, Petrov D, Barres BA, Duncan L, Abyzov A, Vogel H, Moran J, Vaccarino F, Tamminga C, Levinson D, Urban A. Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia. Nature Neuroscience 2021, 24: 186-196. PMID: 33432196, PMCID: PMC8806165, DOI: 10.1038/s41593-020-00767-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultCation Transport ProteinsEmbryonic DevelopmentFemaleGenomeHeLa CellsHigh-Throughput Nucleotide SequencingHumansLong Interspersed Nucleotide ElementsMachine LearningMental DisordersMutagenesis, InsertionalNeurogliaNeuronsPregnancyRetroelementsSchizophreniaConceptsBrain developmentPossible pathological effectsAnatomical distributionBilateral distributionHuman neuronsNervous systemHuman nervous systemNeuropsychiatric diseasesNeuropsychiatric disordersGliaPathological effectsNeuronsSomatic L1 insertionsWhole-genome sequencingHuman brainSomatic retrotransposition
2020
Complex mosaic structural variations in human fetal brains
Sekar S, Tomasini L, Proukakis C, Bae T, Manlove L, Jang Y, Scuderi S, Zhou B, Kalyva M, Amiri A, Mariani J, Sedlazeck F, Urban AE, Vaccarino F, Abyzov A. Complex mosaic structural variations in human fetal brains. Genome Research 2020, 30: gr.262667.120. PMID: 33122304, PMCID: PMC7706730, DOI: 10.1101/gr.262667.120.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsCopy number variantsStructural variantsMegabase-scale copy number variantsHuman fetal brainFunctional consequencesMobile element insertionsSimilar functional consequencesFetal brainMosaic single-nucleotide variantsAdult brain neuronsStructural variationsPotential functional consequencesKilobase scaleDNA eventsGenomic fragmentDifferent chromosomesElement insertionsClonal approachHuman brain cellsFetal human brainNucleotide variantsReplication errorsHuman brainNumber variantsAntibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2018
iPSC-derived neurons profiling reveals GABAergic circuit disruption and acetylated α-tubulin defect which improves after iHDAC6 treatment in Rett syndrome
Landucci E, Brindisi M, Bianciardi L, Catania LM, Daga S, Croci S, Frullanti E, Fallerini C, Butini S, Brogi S, Furini S, Melani R, Molinaro A, Lorenzetti FC, Imperatore V, Amabile S, Mariani J, Mari F, Ariani F, Pizzorusso T, Pinto AM, Vaccarino FM, Renieri A, Campiani G, Meloni I. iPSC-derived neurons profiling reveals GABAergic circuit disruption and acetylated α-tubulin defect which improves after iHDAC6 treatment in Rett syndrome. Experimental Cell Research 2018, 368: 225-235. PMID: 29730163, PMCID: PMC9410763, DOI: 10.1016/j.yexcr.2018.05.001.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsRett syndromeCircuit disruptionΑ-tubulin deacetylaseNew therapeutic strategiesClassic Rett syndromeCommon neurodevelopmental disorderAcetylated α-tubulinEpileptic behaviorTherapeutic strategiesPathogenic mechanismsPluripotent stem cellsCytoskeleton dynamicsGenetic reprogrammingSyndromeTranscriptome changesRNA-seqNeurodevelopmental disordersSignificant decreaseNeuronsSelective inhibitorPatientsMECP2 geneΑ-tubulinTreatment
2015
Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1+/− patients and in foxg1+/− mice
Patriarchi T, Amabile S, Frullanti E, Landucci E, Lo Rizzo C, Ariani F, Costa M, Olimpico F, W Hell J, M Vaccarino F, Renieri A, Meloni I. Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1+/− patients and in foxg1+/− mice. European Journal Of Human Genetics 2015, 24: 871-880. PMID: 26443267, PMCID: PMC4820038, DOI: 10.1038/ejhg.2015.216.Peer-Reviewed Original ResearchConceptsRett syndromeSynaptic markersInhibitory synapsesExcitatory/inhibitory balanceSynaptic protein expressionFetal mouse brainInhibitory synaptic markersPathogenesis of RTTExcitatory synaptic markersSevere neurodevelopmental disorderGlutamatergic markersInhibitory balanceAdult brainAdult micePrecise molecular mechanismsSynaptic differentiationPatientsMouse brainBrain synapsesPathological eventsNeuronsProtein expressionBrainGluD1Neurodevelopmental disordersContribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development
Salmaso N, Dominguez M, Kravitz J, Komitova M, Vaccarino FM, Schwartz ML. Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development. Neuroscience Letters 2015, 604: 12-17. PMID: 26222256, PMCID: PMC4568169, DOI: 10.1016/j.neulet.2015.07.033.Peer-Reviewed Original ResearchConceptsBrain weightEffects of hypoxiaDam exposureCortical volumeBody weightHypoxic conditionsBrain developmentChronic postnatal hypoxiaLow birth weightPup body weightSame hypoxic conditionsChronic hypoxia exposureEarly postnatal pupsBody weight conditionsHypoxic mothersNeurological sequelaePostnatal hypoxiaPremature infantsHypoxic pupsBirth weightChronic hypoxiaHypoxic chamberHypoxic exposureLive birthsMouse modelFOXG1-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 culturesAltered expression of neuropeptides in FoxG1-null heterozygous mutant mice
Frullanti E, Amabile S, Lolli MG, Bartolini A, Livide G, Landucci E, Mari F, Vaccarino FM, Ariani F, Massimino L, Renieri A, Meloni I. Altered expression of neuropeptides in FoxG1-null heterozygous mutant mice. European Journal Of Human Genetics 2015, 24: 252-257. PMID: 25966633, PMCID: PMC4717204, DOI: 10.1038/ejhg.2015.79.Peer-Reviewed Original ResearchConceptsBasal gangliaAdult brainParvalbumin-positive GABAergic interneuronsNeonatal brain developmentWild-type littermatesGroup of neuropeptidesHeterozygous mutant miceHippocampal neurogenesisImpaired social interactionCalcium-dependent signalingTotal brainGABAergic interneuronsNeuronal excitabilityControl of movementHippocampal neuronsArginine vasopressinBehavioral impairmentsWhole brainMammalian forebrainHeterozygous miceMutant miceFOXG1 geneBrain developmentBrainAltered expression
2014
Transcriptome Analysis of the Human Striatum in Tourette Syndrome
Lennington JB, Coppola G, Kataoka-Sasaki Y, Fernandez TV, Palejev D, Li Y, Huttner A, Pletikos M, Sestan N, Leckman JF, Vaccarino FM. Transcriptome Analysis of the Human Striatum in Tourette Syndrome. Biological Psychiatry 2014, 79: 372-382. PMID: 25199956, PMCID: PMC4305353, DOI: 10.1016/j.biopsych.2014.07.018.Peer-Reviewed Original ResearchConceptsCopy number variantsGenome-wide association studiesGene coexpression modulesNumber variantsGene network analysisCommon genetic variantsCoexpression modulesUpregulated genesMetabolism modulesImmune-related genesNetwork analysisAssociation studiesDifferential expressionUpregulated modulesGenetic variantsGenesPatient's striatumTS individualsTranscriptomeVariantsMetabolic alterationsSame regionGamma-aminobutyric acidergic interneuronsTranscriptsRNA
2013
Cortical Gyrification Induced by Fibroblast Growth Factor 2 in the Mouse Brain
Rash BG, Tomasi S, Lim HD, Suh CY, Vaccarino FM. Cortical Gyrification Induced by Fibroblast Growth Factor 2 in the Mouse Brain. Journal Of Neuroscience 2013, 33: 10802-10814. PMID: 23804101, PMCID: PMC3693057, DOI: 10.1523/jneurosci.3621-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolitesAxonsBrain ChemistryBromodeoxyuridineCell CountCerebral CortexCerebral VentriclesDensitometryDependovirusDNA, ComplementaryFemaleFibroblast Growth Factor 2Green Fluorescent ProteinsImmunohistochemistryIn Situ HybridizationLymphoid Enhancer-Binding Factor 1MiceNeocortexPregnancyReal-Time Polymerase Chain ReactionRNAWnt3A ProteinConceptsVentricular zoneIntermediate neuronal progenitorsSubventricular zoneCortical gyrificationCortical primordiumRegion-specific actionsFibroblast growth factor-2ER81 expressionGrowth factor 2Ventricular injectionCortical layer structureBasal radial gliaCortical gyriRadial gliaMouse brainCortical hemEmbryonic day 11.5Neuronal progenitorsGyrus formationLEF1 expressionGyrificationNeurogenesisLissencephalic speciesFactor 2Impaired growth
2012
Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas
Naumova OY, Palejev D, Vlasova NV, Lee M, Rychkov SY, Babich ON, Vaccarino F, Grigorenko EL. Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas. Development And Psychopathology 2012, 24: 1427-1442. PMID: 23062308, PMCID: PMC3539811, DOI: 10.1017/s0954579412000818.Peer-Reviewed Original ResearchConceptsRNA-seqGene expressionAge-related transcriptional changesGene expression profilingCortical areasTranscriptional changesMolecular mechanismsTranscriptomeCentral nervous systemDistinct cortical areasAge-related changesDifferent cellsElderly individualsNervous systemExpressionAge-related variabilityNerve impulsesBrainPreliminary dataNeocortexHuman brainDevelopmental changesDifferent agesDistinct areasDifferentiationPrenatal stress delays inhibitory neuron progenitor migration in the developing neocortex
Stevens HE, Su T, Yanagawa Y, Vaccarino FM. Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex. Psychoneuroendocrinology 2012, 38: 509-521. PMID: 22910687, PMCID: PMC3532962, DOI: 10.1016/j.psyneuen.2012.07.011.Peer-Reviewed Original ResearchEnvironmental Enrichment Increases the GFAP+ Stem Cell Pool and Reverses Hypoxia-Induced Cognitive Deficits in Juvenile Mice
Salmaso N, Silbereis J, Komitova M, Mitchell P, Chapman K, Ment LR, Schwartz ML, Vaccarino FM. Environmental Enrichment Increases the GFAP+ Stem Cell Pool and Reverses Hypoxia-Induced Cognitive Deficits in Juvenile Mice. Journal Of Neuroscience 2012, 32: 8930-8939. PMID: 22745493, PMCID: PMC3399175, DOI: 10.1523/jneurosci.1398-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAnimals, NewbornBromodeoxyuridineCell CountCell DifferentiationCognition DisordersDeoxyuridineDisease Models, AnimalEnvironmentEstrogen AntagonistsFemaleGene Expression Regulation, DevelopmentalGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsHumansHypoxiaIdoxuridineKi-67 AntigenMaleMaze LearningMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeurogenesisNeurogliaReceptors, EstrogenStem CellsTamoxifenConceptsHypoxic injuryBrain injuryAstroglial cellsChronic hypoxic injuryDevelopmental brain injuryLow birth weightCell poolEnvironmental enrichmentAdult brain injuryAbnormal lung developmentStem cell poolPerinatal hypoxic injuryFate-mapping modelsSocio-demographic factorsNeurobiological recoveryHippocampal neurogenesisVLBW cohortPremature childrenBirth weightCardiovascular abnormalitiesJuvenile miceAnimal modelsLung developmentInjuryCognitive deficitsLearning and Memory Depend on Fibroblast Growth Factor Receptor 2 Functioning in Hippocampus
Stevens HE, Jiang GY, Schwartz ML, Vaccarino FM. Learning and Memory Depend on Fibroblast Growth Factor Receptor 2 Functioning in Hippocampus. Biological Psychiatry 2012, 71: 1090-1098. PMID: 22541947, PMCID: PMC3371339, DOI: 10.1016/j.biopsych.2012.03.013.Peer-Reviewed Original ResearchConceptsFGF receptor 2Fibroblast growth factorDentate gyrusReceptor 2Embryonic knockoutWater maze probe trialGrowth factor receptor 2Reference memoryFactor receptor 2Spatial reference memoryNeural stem cellsFibroblast growth factor receptor 2Immature neuronsCortical neuronsHippocampal volumeInducible knockout miceParvalbumin interneuronsShort-term learningGranule cellsKnockout miceSeparate cellular componentsHippocampusLong-term reference memoryAdult spatial memoryGrowth factorImpaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice
Smith K, Williamson TL, Schwartz ML, Vaccarino FM. Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice. Brain Research 2012, 1460: 12-24. PMID: 22578469, PMCID: PMC3361544, DOI: 10.1016/j.brainres.2012.04.002.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorHuman GFAP promoterInner granule cell layerDKO miceGranule cell numberGranule cell progenitorsRadial glial stem cellsMidline glial structuresImpaired motor coordinationCerebellar sizeGranule cell layerDouble knockout miceGlial precursor cellsGlial stem cellsCell numberGranule neuron precursorsGrowth factor receptorGABA interneuronsGranule cell migrationCerebral cortexExternal granular layerMolecular layerMotor coordinationGranule cellsKnockout mice
2011
Annual 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
Fgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits
Stevens HE, Smith KM, Maragnoli ME, Fagel D, Borok E, Shanabrough M, Horvath TL, Vaccarino FM. Fgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits. Journal Of Neuroscience 2010, 30: 5590-5602. PMID: 20410112, PMCID: PMC2868832, DOI: 10.1523/jneurosci.5837-09.2010.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexCerebral cortexFibroblast growth factor receptorCKO miceExcitatory neuronsPrefrontal cortexCortical neuron developmentEntire cerebral cortexRadial glial cellsSpecific fibroblast growth factor receptorsGrowth factor receptorGABAergic neuronsLimbic circuitsCortical neuronsGlial cellsSubcortical stationsBed nucleusCortical developmentLimbic systemStria terminalisSynaptic terminalsSecondary decreaseNeuronal precursorsVentricular zoneNeuron development