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 changesAlterationsEarly Neuronal Differentiation/patterning of the Human Pallium, Modeling by in Vitro Systems, and Disruption in Developmental Disorders
Scuderi S, Jourdon A, Vaccarino F. Early Neuronal Differentiation/patterning of the Human Pallium, Modeling by in Vitro Systems, and Disruption in Developmental Disorders. 2023, 423-442. DOI: 10.1002/9781119860914.ch20.Peer-Reviewed Original ResearchCentral nervous systemDorsal-anterior partHuman cortexCortical developmentInhibitory neuronsSingle-cell omicsAnimal modelsNervous systemCortical layersMammalian brainBrain regionsCortical formationPopulations of excitatoryTangential migrationAltered developmentCortical structuresAnterior partCortical patterningPrecursor cellsEarly neuronal differentiationIncoming afferentsCortexNeuronal differentiationNeuronsHuman specificity
2021
Machine 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
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
2017
Human induced pluripotent stem cells for modelling neurodevelopmental disorders
Ardhanareeswaran K, Mariani J, Coppola G, Abyzov A, Vaccarino FM. Human induced pluripotent stem cells for modelling neurodevelopmental disorders. Nature Reviews Neurology 2017, 13: 265-278. PMID: 28418023, PMCID: PMC5782822, DOI: 10.1038/nrneurol.2017.45.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEmbryonic stem cellsNeurodevelopmental disordersPluripotent stem cellsBrain developmentStem cellsAbnormal brain developmentBrain cell typesDopaminergic neuronsCortical neuronsUnique genetic signatureEarly developmentKey PointsHumanHiPSC modelsSomatic cellsDisordersGenetic signaturesGenetic studiesAltered trajectoryCell typesAdult cellsNeuronsUnknown facetsCellsDrug discoveryHiPSCs
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 disorders
2014
Leptin 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
2011
Cortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury
Bi B, Salmaso N, Komitova M, Simonini MV, Silbereis J, Cheng E, Kim J, Luft S, Ment LR, Horvath TL, Schwartz ML, Vaccarino FM. Cortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury. Journal Of Neuroscience 2011, 31: 9205-9221. PMID: 21697371, PMCID: PMC3142780, DOI: 10.1523/jneurosci.0518-11.2011.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic protein-positive cellsCortical excitatory neuronsProtein-positive cellsPerinatal hypoxic injuryPostnatal hypoxiaGenetic fate mappingCortical astrogliaPremature childrenHypoxic injuryBrain injuryNew neuronsPreterm childrenNeurogenic nicheCognitive recoveryExcitatory neuronsGenerate neuronsNeuronal fateNeuronsHypoxiaCortical parenchymaInjuryParenchymaFate mappingCellsChildren
2010
Pyramidal Neurons Are Generated from Oligodendroglial Progenitor Cells in Adult Piriform Cortex
Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, Pleasure D. Pyramidal Neurons Are Generated from Oligodendroglial Progenitor Cells in Adult Piriform Cortex. Journal Of Neuroscience 2010, 30: 12036-12049. PMID: 20826667, PMCID: PMC2940828, DOI: 10.1523/jneurosci.1360-10.2010.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsAntigensAntineoplastic Agents, HormonalBromodeoxyuridineCell CountCell DifferentiationCerebral CortexDoublecortin Domain ProteinsDrug Administration ScheduleEye ProteinsGene Expression RegulationGreen Fluorescent ProteinsHomeodomain ProteinsMiceMice, Inbred C57BLMice, TransgenicMicrotubule-Associated ProteinsMyelin Proteolipid ProteinNerve Tissue ProteinsNeuronsNeuropeptidesOligodendrogliaPaired Box Transcription FactorsPAX6 Transcription FactorProteoglycansPyramidal CellsReceptor, Platelet-Derived Growth Factor alphaReceptors, N-Methyl-D-AspartateRepressor ProteinsSOXB1 Transcription FactorsTamoxifenTime FactorsConceptsOligodendroglial progenitor cellsPyramidal glutamatergic neuronsPiriform cortexAdult piriform cortexGlutamatergic neuronsCortical glutamatergic neuronsProgenitor cellsNeural stem cell markersCortical neuronal networksStem cell markersTranscription factor characteristicImmature neuronsCerebral cortexPyramidal neuronsCell markersCortexNeuronsCre-loxP recombination systemNeuronal networksLines of evidenceMarkersLow levelsCellsPrevious studiesDoublecortin
2007
Astroglial Cells in Development, Regeneration, and Repair
Vaccarino FM, Fagel DM, Ganat Y, Maragnoli ME, Ment LR, Ohkubo Y, Schwartz ML, Silbereis J, Smith KM. Astroglial Cells in Development, Regeneration, and Repair. The Neuroscientist 2007, 13: 173-185. PMID: 17404377, DOI: 10.1177/1073858406298336.Peer-Reviewed Original Research In PressConceptsFibroblast growth factor receptorAstroglial cellsGenetic fate mappingCell divisionLineage studiesGrowth factor receptorPostnatal CNSEmbryonic CNSMain cellular componentsFate mappingNeuronal differentiationCellular componentsCell typesInjury-induced increaseFactor receptorNeurogenic nichePerinatal injuryCerebral cortexYoung miceCellsOligodendrocytesNeuronsDifferent rolesCNSNiche
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 recombinase
1999
Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene
Acampora D, Postiglione M, Avantaggiato V, Di Bonito M, Vaccarino F, Michaud J, Simeone A. Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Genes & Development 1999, 13: 2787-2800. PMID: 10557207, PMCID: PMC317121, DOI: 10.1101/gad.13.21.2787.Peer-Reviewed Original ResearchConceptsCorticotropin-releasing hormoneAnterior periventricularProgressive impairmentArginine vasopressinHypothalamus of miceTerminal differentiationNeuroendocrine cell lineagesCell lineagesNeuronal cell lineagesMagnocellular neuronsNeuroendocrine hypothalamusAbnormal cell migrationParaventricularCell proliferationHypothalamusCell migrationMiceBRN2 expressionNeuronsImpairmentOxytocinPeriventricularDifferentiation
1995
Basic Fibroblast Growth Factor Increases the Number of Excitatory Neurons Containing Glutamate in the Cerebral Cortex
Vaccarino F, Schwartz M, Hartigan D, Leckman J. Basic Fibroblast Growth Factor Increases the Number of Excitatory Neurons Containing Glutamate in the Cerebral Cortex. Cerebral Cortex 1995, 5: 64-78. PMID: 7719131, DOI: 10.1093/cercor/5.1.64.Peer-Reviewed Original ResearchConceptsBasic fibroblast growth factorNerve growth factorGlutamate-containing neuronsCerebral cortexFibroblast growth factorGrowth factorAspartate-containing neuronsDifferent neurotransmitter phenotypesNumber of GABARatio of glutamateStem cellsNeurotransmitter phenotypeExcitatory neuronsInhibitory neuronsRat telencephalonVentricular zoneBFGF mRNAGABANeuronsCortexGlutamateDiffusible factorsThreefold increaseCellsFactors
1987
Subcellular Location and Neuronal Release of Diazepam Binding Inhibitor
Ferrarese C, Vaccarino F, Alho H, Mellstrom B, Costa E, Guidotti A. Subcellular Location and Neuronal Release of Diazepam Binding Inhibitor. Journal Of Neurochemistry 1987, 48: 1093-1102. PMID: 3819722, DOI: 10.1111/j.1471-4159.1987.tb05632.x.Peer-Reviewed Original ResearchConceptsDBI-like immunoreactivitySlices of hypothalamusCerebral cortical neuronsGamma-aminobutyric acid receptorsRat brain neuronsDiazepam binding inhibitorAllosteric modulatory sitesVeratridine depolarizationNeuronal releaseCerebral cortexMicroM tetrodotoxinSlices of liverPeripheral organsCNS neuronsCortical neuronsBinding of benzodiazepinesCortical astrocytesBrain neuronsNeuromodulatory substancesRat brainSynaptosomal lysatesModulatory siteMet5-enkephalinAcid receptorsNeurons
1986
Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures.
Vicini S, Alho H, Costa E, Mienville JM, Santi MR, Vaccarino FM. Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures. Proceedings Of The National Academy Of Sciences Of The United States Of America 1986, 83: 9269-9273. PMID: 3097650, PMCID: PMC387117, DOI: 10.1073/pnas.83.23.9269.Peer-Reviewed Original ResearchConceptsInhibitory synaptic currentsSynaptic currentsRo 15Whole-cell patch-clamp techniqueActions of flunitrazepamGamma-aminobutyric acid receptorsNeonatal rat cortexCortical cell culturesPatch-clamp techniqueImidazobenzodiazepine Ro 15High-affinity ligandsRat cortexSynaptic transmissionPostsynaptic cellElectrical stimulationEndogenous ligandAcid receptorsImmunocytochemical stainingPrimary culturesNeuronsFlunitrazepamCell culturesIntrinsic activityDerivative methylAllosteric regulatory site