2024
Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids
Capauto D, Wang Y, Wu F, Norton S, Mariani J, Inoue F, Crawford G, Ahituv N, Abyzov A, Vaccarino F. Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids. Scientific Reports 2024, 14: 3936. PMID: 38365907, PMCID: PMC10873509, DOI: 10.1038/s41598-024-54302-7.Peer-Reviewed Original ResearchConceptsMassively parallel reporter assaysGene expressionRegulation of gene expressionForebrain organoidsHuman fetal tissuesHigh-throughput assayReporter assayFetal tissuesStem cellsNeurodevelopmentHuman neurodevelopmentActivation signalsEnhanced activityGenesOrganoidsForebrainBrain organoidsAssayBrain
2022
Mispatterning 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 stagesCholinergicPatientsA nomenclature consensus for nervous system organoids and assembloids
Pașca SP, Arlotta P, Bateup HS, Camp JG, Cappello S, Gage FH, Knoblich JA, Kriegstein AR, Lancaster MA, Ming GL, Muotri AR, Park IH, Reiner O, Song H, Studer L, Temple S, Testa G, Treutlein B, Vaccarino FM. A nomenclature consensus for nervous system organoids and assembloids. Nature 2022, 609: 907-910. PMID: 36171373, PMCID: PMC10571504, DOI: 10.1038/s41586-022-05219-6.Peer-Reviewed Original Research
2020
PsychENCODE and beyond: transcriptomics and epigenomics of brain development and organoids
Jourdon A, Scuderi S, Capauto D, Abyzov A, Vaccarino FM. PsychENCODE and beyond: transcriptomics and epigenomics of brain development and organoids. Neuropsychopharmacology 2020, 46: 70-85. PMID: 32659782, PMCID: PMC7689467, DOI: 10.1038/s41386-020-0763-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRecent single-cell technologiesGene regulatory networksSingle-cell technologiesMulti-omics investigationsPluripotent stem cellsTranscriptional dynamicsBrain developmentCell fateEpigenomic datasetsRegulatory networksElement activityNeural lineagesStem cellsBrain organoidsOrganoidsBiological modelsFetal brainPsychENCODEBrain biologyMajor questionsEpigenomicsFetal tissuesTranscriptomicsLineagesBiologyChapter 5 Induced pluripotent stem cells as models of human neurodevelopmental disorders
Jourdon A, Mariani J, Scuderi S, Amiri A, Wu F, Yuen E, Abyzov A, Vaccarino F. Chapter 5 Induced pluripotent stem cells as models of human neurodevelopmental disorders. 2020, 99-127. DOI: 10.1016/b978-0-12-814409-1.00005-7.ChaptersPluripotent stem cellsStem cellsStudy of speciesHuman neurodevelopmental disordersEpigenome analysisGene regulationIPSC fieldGenomic variationGene expressionGenetic backgroundDisease modelingStudies of neurodevelopmentIPSCsExperimental approachNeurodevelopmental disordersTranscriptomeGenomeCellsCell phenotypingSpeciesExperimental design issuesPhenotypeRegulationExpressionPhenotyping
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
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 culturesThe use of stem cells to study autism spectrum disorder.
Ardhanareeswaran K, Coppola G, Vaccarino F. The use of stem cells to study autism spectrum disorder. The Yale Journal Of Biology And Medicine 2015, 88: 5-16. PMID: 25745370, PMCID: PMC4345539.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman-induced pluripotent stem cellsStem cellsNeuronal developmentIdentification of hundredsEmbryonic stem cellsUnique genetic signaturePluripotent stem cellsCore symptomsASD patientsAutism spectrum disorderPost-mortem brain samplesGenome studiesGenetic signaturesAutism core symptomsNew therapeutic avenuesSerious developmental disabilitiesIdiopathic autism spectrum disorderSkin biopsiesHuman-specific behaviorsSpectrum disorderSingle drugDrug AdministrationTherapeutic avenuesBrain samplesDiagnostic tests
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 ResearchNeurobiology meets genomic science: The promise of human-induced pluripotent stem cells
Stevens HE, Mariani J, Coppola G, Vaccarino FM. Neurobiology meets genomic science: The promise of human-induced pluripotent stem cells. Development And Psychopathology 2012, 24: 1443-1451. PMID: 23062309, PMCID: PMC3513939, DOI: 10.1017/s095457941200082x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman-induced pluripotent stem cellsPluripotent stem cellsStem cellsNeuronal cellsInduced pluripotent stem cell (iPSC) technologyPluripotent stem cell (iPSC) technologyNormal human brain developmentHuman genesSomatic cellsCell biologyStem cell technologyGene transcriptsHuman brain developmentAspects of developmentMessenger RNADevelopmental stepsGenomic scienceBiologySeries of eventsCellsBrain developmentGenesGeneticsHuman individualsTranscriptsModeling 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
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
2004
Fibroblast Growth Factor Receptor 1 Is Required for the Proliferation of Hippocampal Progenitor Cells and for Hippocampal Growth in Mouse
Ohkubo Y, Uchida AO, Shin D, Partanen J, Vaccarino FM. Fibroblast Growth Factor Receptor 1 Is Required for the Proliferation of Hippocampal Progenitor Cells and for Hippocampal Growth in Mouse. Journal Of Neuroscience 2004, 24: 6057-6069. PMID: 15240797, PMCID: PMC6729672, DOI: 10.1523/jneurosci.1140-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationCell CountCell LineageCell ProliferationCells, CulturedHeredodegenerative Disorders, Nervous SystemHippocampusHumansIn Situ HybridizationLateral VentriclesMiceMice, TransgenicMutagenesis, Site-DirectedNeurogliaNeuronsPyramidal CellsReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorRNA, MessengerStem CellsTransgenesConceptsHippocampal ventricular zonesDentate gyrusGrowth factor receptor 1Fibroblast growth factor receptor 1Factor receptor 1Ventricular zoneNeural stem cellsPyramidal neuronsHippocampal growthProgenitor cellsGranule cellsReceptor 1Glial fibrillary acidic protein promoterHuman glial fibrillary acidic protein promoterEmbryonic dorsal telencephalonRadial glial-like cellsRadial glial progenitor cellsHippocampal dentate gyrusParvalbumin-containing interneuronsDG granule cellsHippocampal pyramidal neuronsStem cellsHippocampal progenitor cellsRole of FGFR1Glial progenitor cellsFibroblast Growth Factor 2 Is Required for Maintaining the Neural Stem Cell Pool in the Mouse Brain Subventricular Zone
Zheng W, Nowakowski RS, Vaccarino FM. Fibroblast Growth Factor 2 Is Required for Maintaining the Neural Stem Cell Pool in the Mouse Brain Subventricular Zone. Developmental Neuroscience 2004, 26: 181-196. PMID: 15711059, DOI: 10.1159/000082136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBrainCell Cycle ProteinsCell DifferentiationCell DivisionCell LineageCell ProliferationCerebral CortexDown-RegulationImmunohistochemistryLateral VentriclesMiceMice, KnockoutNeurogliaNeuronsOlfactory BulbReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 2Receptors, Fibroblast Growth FactorStem CellsConceptsStem cell poolNeural stem cellsFgf2 knockout miceSlower cell cycle kineticsProgenitor cell populationsSubventricular zoneCell poolNeural stem cell poolGene productsProgenitor populationsFibroblast growth factor-2Olfactory bulbKnockout miceCell cycleOlfactory bulb neurogenesisMolecular markersSmaller olfactory bulbsGrowth factor 2Brain subventricular zoneAnterior subventricular zoneReceptor proteinGlial fibrillary acidic proteinCell cycle kineticsStem cellsFibrillary acidic protein
2001
Stem Cells in Neurodevelopment and Plasticity
Vaccarino F, Ganat Y, Zhang Y, Zheng W. Stem Cells in Neurodevelopment and Plasticity. Neuropsychopharmacology 2001, 25: 805-815. PMID: 11750175, DOI: 10.1016/s0893-133x(01)00349-9.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsTranscription factorsProgenitor cellsEpidermal growth factor EGFGrowth factors FGF2Stem cell proliferationGrowth factors EGFPostnatal central nervous systemNuclear transcription factorTranscriptional programsGenetic programGene cascadeNeuronal fateCell-surface interactionsControl proliferationPool of cellsCentral nervous systemEnvironmental perturbationsAdult central nervous systemMolecular signaturesDividing cellsStem cellsCell proliferationEmbryogenesisCell interactions
2000
Stem Cells and Neuronal Progenitors and Their Diversity in the CNS: Are Time and Place Important?
Vaccarino F. Stem Cells and Neuronal Progenitors and Their Diversity in the CNS: Are Time and Place Important? The Neuroscientist 2000, 6: 338-352. DOI: 10.1177/107385840000600508.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsDifferent cell typesFibroblast growth factorStem cellsTranscription factorsEarly transcriptional regulatorCell typesHelix transcription factorHomeodomain transcription factorPattern of expressionMultilineage progenitor cellsTranscriptional regulatorsFounder cellsCellular repertoireExtracellular signalsProper assemblyNeuronal progenitorsPositional specificationBasic fibroblast growth factorBody axesImmediate progenyProgenitor cellsGrowth factorRegulatorCellsCNS domains
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