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 changesAlterations
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 ResearchCell-to-Cell Adhesion and Neurogenesis in Human Cortical Development: A Study Comparing 2D Monolayers with 3D Organoid Cultures
Scuderi S, Altobelli GG, Cimini V, Coppola G, Vaccarino FM. Cell-to-Cell Adhesion and Neurogenesis in Human Cortical Development: A Study Comparing 2D Monolayers with 3D Organoid Cultures. Stem Cell Reports 2021, 16: 264-280. PMID: 33513360, PMCID: PMC7878838, DOI: 10.1016/j.stemcr.2020.12.019.Peer-Reviewed Original Research
2020
Antibodies 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
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
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 interneuronsTranscriptsRNALeptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nature Neuroscience 2014, 17: 908-910. PMID: 24880214, PMCID: PMC4113214, DOI: 10.1038/nn.3725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell CountEatingExcitatory Postsynaptic PotentialsGlial Fibrillary Acidic ProteinHypothalamusImmunohistochemistryIn Situ HybridizationLeptinMaleMelanocortinsMiceMice, KnockoutMicroscopy, ElectronNerve NetNeuronsPrimary Cell CulturePro-OpiomelanocortinPulmonary Gas ExchangeReal-Time Polymerase Chain ReactionRNA, MessengerSignal Transduction
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 ResearchPrenatal 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
2009
Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome
Kataoka Y, Kalanithi PS, Grantz H, Schwartz ML, Saper C, Leckman JF, Vaccarino FM. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. The Journal Of Comparative Neurology 2009, 518: 277-291. PMID: 19941350, PMCID: PMC2846837, DOI: 10.1002/cne.22206.Peer-Reviewed Original ResearchConceptsMedium spiny neuronsCholinergic interneuronsTourette syndromeNormal controlsCholinergic striatal interneuronsNumber of parvalbuminBrains of patientsCaudate nucleus volumeUnbiased stereological analysisStriatal interneuronsOngoing motor behaviorCholinergic cellsTotal neuronsCholine acetyltransferaseSpiny neuronsLimbic regionsStriatum of individualsTS patientsPostmortem brainsThalamic controlSensorimotor regionsInterneuronsCellular abnormalitiesNeuron firingTS subjectsHypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment
Chahboune H, Ment LR, Stewart WB, Rothman DL, Vaccarino FM, Hyder F, Schwartz ML. Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment. Cerebral Cortex 2009, 19: 2891-2901. PMID: 19380380, PMCID: PMC2774398, DOI: 10.1093/cercor/bhp068.Peer-Reviewed Original ResearchConceptsChronic sublethal hypoxiaLow birth weight preterm infantsBirth weight preterm infantsHypoxia-induced modificationNeonatal rodent modelPreterm birth resultsWeight preterm infantsSignificant neurodevelopmental disabilitiesOpen field taskGreater locomotor activityPreterm infantsPreterm birthNeurodevelopmental consequencesBirth resultsHypoxic injurySomatosensory cortexCaudate putamenCallosal connectivityCorpus callosumBehavioral deficitsNeurodevelopmental disabilitiesRodent modelsNeonatal developmentDTI findingsSublethal hypoxia
2007
Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice
Smith K, Fagel DM, Stevens HE, Rabenstein RL, Maragnoli ME, Ohkubo Y, Picciotto MR, Schwartz ML, Vaccarino FM. Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice. Biological Psychiatry 2007, 63: 953-962. PMID: 17988653, DOI: 10.1016/j.biopsych.2007.09.020.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineAnimalsBehavior, AnimalBiogenic MonoaminesCell CountCentral Nervous System StimulantsCerebral CortexDisease Models, AnimalDopamine AgentsExploratory BehaviorFibroblast Growth Factor 1Glutamate DecarboxylaseHyperkinesisLocomotionMaleMethylphenidateMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsNeural InhibitionNeuronsSignal TransductionConceptsInhibitory cortical circuitsCortical pyramidal neuronsD2 receptor antagonistGrowth factor receptor 1Spontaneous locomotor hyperactivityFibroblast growth factor receptor 1Factor receptor 1Inhibitory neuronal subtypesLocomotor hyperactivityDopamine agonistsCerebral cortexPyramidal neuronsBasal gangliaMotor hyperactivityReceptor antagonistInhibitory interneuronsTyrosine hydroxylaseCortical circuitsPsychiatric disordersLocomotor responseNeuronal subtypesReceptor 1Mutant miceDopamine transporterSpatial learning
2006
Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo
Ganat YM, Silbereis J, Cave C, Ngu H, Anderson GM, Ohkubo Y, Ment LR, Vaccarino FM. Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo. Journal Of Neuroscience 2006, 26: 8609-8621. PMID: 16914687, PMCID: PMC6674357, DOI: 10.1523/jneurosci.2532-06.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesBrainCell DifferentiationCell LineageCerebral VentriclesDoublecortin ProteinFemaleGlial Fibrillary Acidic ProteinHumansIntegrasesMaleMiceMice, TransgenicNeuronsOlfactory BulbOligodendrogliaPromoter Regions, GeneticRecombination, GeneticStem CellsTransgenesConceptsDentate gyrusHuman GFAP promoterCerebral cortexAstroglial cellsSubventricular zoneOlfactory bulbPostnatal brainNeural progenitor/stem cellsPostnatal day 5First postnatal weekProgenitor/stem cellsStem cellsInducible Cre recombinaseNeural stem cellsGenetic fate mappingMature neuronsPostnatal weekCNS regionsWhite matterDay 5GFAP promoterNeural precursorsCortexNeuronsCre recombinaseMidline radial glia translocation and corpus callosum formation require FGF signaling
Smith KM, Ohkubo Y, Maragnoli ME, Rašin M, Schwartz ML, Šestan N, Vaccarino FM. Midline radial glia translocation and corpus callosum formation require FGF signaling. Nature Neuroscience 2006, 9: 787-797. PMID: 16715082, DOI: 10.1038/nn1705.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell MovementCell ShapeCerebral CortexCorpus CallosumDown-RegulationFemaleFibroblast Growth Factor 8Fibroblast Growth FactorsGrowth ConesMaleMiceMice, KnockoutMice, TransgenicNeurogliaReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2RNA InterferenceSignal TransductionConceptsRadial glial cellsGlial cellsSomal translocationRadial gliaCorpus callosum formationReceptor 1 geneCallosal dysgenesisCerebral cortexFibroblast growth factor receptor 1 (FGFR1) geneIndusium griseumDorsomedial cortexDorsolateral cortexKnockout miceCortexAstrogliaApical endfeetFGFR1 geneAstrocytesGliaAxon guidanceDorsal midlinePrecise targetingCellsUnexpected roleFGF