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 ResearchMeSH KeywordsEnhancer Elements, GeneticGene Expression RegulationHumansOrganoidsProsencephalonRegulatory Sequences, Nucleic AcidConceptsMassively parallel reporter assaysGene expressionRegulation of gene expressionForebrain organoidsHuman fetal tissuesHigh-throughput assayReporter assayFetal tissuesStem cellsNeurodevelopmentHuman neurodevelopmentActivation signalsEnhanced activityGenesOrganoidsForebrainBrain organoidsAssayBrain
2022
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Bae T, Fasching L, Wang Y, Shin JH, Suvakov M, Jang Y, Norton S, Dias C, Mariani J, Jourdon A, Wu F, Panda A, Pattni R, Chahine Y, Yeh R, Roberts RC, Huttner A, Kleinman JE, Hyde TM, Straub RE, Walsh CA, Urban A, Leckman J, Weinberger D, Vaccarino F, Abyzov A, Walsh C, Park P, Sestan N, Weinberger D, Moran J, Gage F, Vaccarino F, Gleeson J, Mathern G, Courchesne E, Roy S, Chess A, Akbarian S, Bizzotto S, Coulter M, Dias C, D’Gama A, Ganz J, Hill R, Huang A, Khoshkhoo S, Kim S, Lee A, Lodato M, Maury E, Miller M, Borges-Monroy R, Rodin R, Zhou Z, Bohrson C, Chu C, Cortes-Ciriano I, Dou Y, Galor A, Gulhan D, Kwon M, Luquette J, Sherman M, Viswanadham V, Jones A, Rosenbluh C, Cho S, Langmead B, Thorpe J, Erwin J, Jaffe A, McConnell M, Narurkar R, Paquola A, Shin J, Straub R, Abyzov A, Bae T, Jang Y, Wang Y, Molitor C, Peters M, Linker S, Reed P, Wang M, Urban A, Zhou B, Zhu X, Pattni R, Serres Amero A, Juan D, Lobon I, Marques-Bonet T, Solis Moruno M, Garcia Perez R, Povolotskaya I, Soriano E, Antaki D, Averbuj D, Ball L, Breuss M, Yang X, Chung C, Emery S, Flasch D, Kidd J, Kopera H, Kwan K, Mills R, Moldovan J, Sun C, Zhao X, Zhou W, Frisbie T, Cherskov A, Fasching L, Jourdon A, Pochareddy S, Scuderi S. Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability. Science 2022, 377: 511-517. PMID: 35901164, PMCID: PMC9420557, DOI: 10.1126/science.abm6222.Peer-Reviewed Original ResearchMeSH KeywordsAgingAutistic DisorderBrainEnhancer Elements, GeneticGene Expression RegulationHumansMutagenesisMutationProtein BindingTranscription FactorsWhole Genome SequencingConceptsTranscription factorsSomatic mutationsPutative transcription factorEnhancer-like regionSingle nucleotide mutationsWhole-genome sequencingGene regulationSomatic duplicationGenome sequencingDamaging mutationsBackground mutagenesisMutationsHypermutabilityClonal expansionMotifDiseased brainPotential linkVivo clonal expansionMutagenesisGenesDuplicationSequencingRegulation
2018
Comprehensive functional genomic resource and integrative model for the human brain
Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, Clarke D, Gu M, Emani P, Yang YT, Xu M, Gandal MJ, Lou S, Zhang J, Park JJ, Yan C, Rhie SK, Manakongtreecheep K, Zhou H, Nathan A, Peters M, Mattei E, Fitzgerald D, Brunetti T, Moore J, Jiang Y, Girdhar K, Hoffman GE, Kalayci S, Gümüş ZH, Crawford GE, Roussos P, Akbarian S, Jaffe A, White K, Weng Z, Sestan N, Geschwind D, Knowles J, Gerstein M, Ashley-Koch A, Crawford G, Garrett M, Song L, Safi A, Johnson G, Wray G, Reddy T, Goes F, Zandi P, Bryois J, Jaffe A, Price A, Ivanov N, Collado-Torres L, Hyde T, Burke E, Kleiman J, Tao R, Shin J, Akbarian S, Girdhar K, Jiang Y, Kundakovic M, Brown L, Kassim B, Park R, Wiseman J, Zharovsky E, Jacobov R, Devillers O, Flatow E, Hoffman G, Lipska B, Lewis D, Haroutunian V, Hahn C, Charney A, Dracheva S, Kozlenkov A, Belmont J, DelValle D, Francoeur N, Hadjimichael E, Pinto D, van Bakel H, Roussos P, Fullard J, Bendl J, Hauberg M, Mangravite L, Peters M, Chae Y, Peng J, Niu M, Wang X, Webster M, Beach T, Chen C, Jiang Y, Dai R, Shieh A, Liu C, Grennan K, Xia Y, Vadukapuram R, Wang Y, Fitzgerald D, Cheng L, Brown M, Brown M, Brunetti T, Goodman T, Alsayed M, Gandal M, Geschwind D, Won H, Polioudakis D, Wamsley B, Yin J, Hadzic T, De La Torre Ubieta L, Swarup V, Sanders S, State M, Werling D, An J, Sheppard B, Willsey A, White K, Ray M, Giase G, Kefi A, Mattei E, Purcaro M, Weng Z, Moore J, Pratt H, Huey J, Borrman T, Sullivan P, Giusti-Rodriguez P, Kim Y, Sullivan P, Szatkiewicz J, Rhie S, Armoskus C, Camarena A, Farnham P, Spitsyna V, Witt H, Schreiner S, Evgrafov O, Knowles J, Gerstein M, Liu S, Wang D, Navarro F, Warrell J, Clarke D, Emani P, Gu M, Shi X, Xu M, Yang Y, Kitchen R, Gürsoy G, Zhang J, Carlyle B, Nairn A, Li M, Pochareddy S, Sestan N, Skarica M, Li Z, Sousa A, Santpere G, Choi J, Zhu Y, Gao T, Miller D, Cherskov A, Yang M, Amiri A, Coppola G, Mariani J, Scuderi S, Szekely A, Vaccarino F, Wu F, Weissman S, Roychowdhury T, Abyzov A. Comprehensive functional genomic resource and integrative model for the human brain. Science 2018, 362 PMID: 30545857, PMCID: PMC6413328, DOI: 10.1126/science.aat8464.Peer-Reviewed Original ResearchConceptsQuantitative trait lociCell type proportionsComprehensive functional genomics resourceExpression quantitative trait lociFunctional genomics resourcesSingle-cell expression profilesGene regulatory networksFurther quantitative trait lociPsychENCODE ConsortiumGenomic resourcesComprehensive online resourceRegulatory networksKey genesCross-population variationExpression profilesMolecular mechanismsCell typesGenesAdult brainPolygenic risk scoresStudy variantsChromatinSplicingGenetic riskInterpretable deep learning model
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
2009
Precursors with Glial Fibrillary Acidic Protein Promoter Activity Transiently Generate GABA Interneurons in the Postnatal Cerebellum
Silbereis J, Cheng E, Ganat YM, Ment LR, Vaccarino FM. Precursors with Glial Fibrillary Acidic Protein Promoter Activity Transiently Generate GABA Interneurons in the Postnatal Cerebellum. Stem Cells 2009, 27: 1152-1163. PMID: 19418461, PMCID: PMC2903623, DOI: 10.1002/stem.18.Peer-Reviewed Original ResearchConceptsCerebellar white matterWhite matterGFAP/Inducible Cre recombinationMolecular layerGlial cell typesNSC/NPCsGABA interneuronsGFAP promoter activityGAD-67GABAergic interneuronsGlial cellsIntact cerebellumNeurogenic potentialCerebellar cortexCerebellar interneuronsInhibitory factorPostnatal cerebellumInterneuronsNeural stemProgenitor cellsDifferent neuronsCerebellumCerebellar developmentCre recombination
1994
Excitatory amino acid receptors in glial progenitor cells: Molecular and functional properties
Gallo V, Patneau D, Mayer M, Vaccarino F. Excitatory amino acid receptors in glial progenitor cells: Molecular and functional properties. Glia 1994, 11: 94-101. PMID: 7927651, DOI: 10.1002/glia.440110204.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCells, CulturedCerebral CortexDNA-Binding ProteinsEarly Growth Response Protein 1Gene Expression RegulationGenes, Immediate-EarlyGlutamic AcidImmediate-Early ProteinsKainic AcidMembrane PotentialsN-MethylaspartateNerve Tissue ProteinsNeurotoxinsOligodendrogliaRatsReceptors, GlutamateStem CellsTranscription FactorsConceptsCG-4 cellsAMPA receptor antagonist CNQXWhole-cell patch-clamp recordingsExcitatory amino acid receptorsProgenitor cellsAmino acid receptorsRat cerebral cortexPatch-clamp recordingsGlial progenitor cellsGlutamate receptor subunitsAgonists L-glutamateGlutamate-gated channelsImmediate early gene NGFIAntagonist CNQXCerebral cortexGABA antibodyPrimary cell linesGlutamate receptorsTransient elevationAcid receptorsReceptor subunitsOligodendrocyte lineageOligodendrocyte progenitorsL-glutamateKainate
1993
Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex
Vaccarino FM, Hayward MD, Le HN, Hartigan DJ, Duman RS, Nestler EJ. Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex. Brain Research 1993, 19: 76-82. PMID: 8103187, DOI: 10.1016/0169-328x(93)90151-e.Peer-Reviewed Original ResearchMeSH Keywords2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepineAnimalsAnimals, NewbornBucladesineCells, CulturedCerebral CortexColforsinCyclic AMPDNA-Binding ProteinsDopamine AgentsEarly Growth Response Protein 1ErgolinesGene Expression RegulationGenes, fosGenes, junGlutamatesGlutamic AcidImmediate-Early ProteinsImmunohistochemistryKineticsNeurogliaNeuronsQuinpiroleRatsRNA, MessengerSecond Messenger SystemsTranscription FactorsVasoactive Intestinal PeptideConceptsVasoactive intestinal peptideRat cerebral cortexCerebral cortexExcitatory amino acid receptor antagonistsDibutyryl cAMPAmino acid receptor antagonistsPrimary culturesC-fosDihydropyridine-sensitive calcium channelsAcid receptor antagonistsIEG inductionCalcium-free mediumCAMP second messenger pathwayIEGs c-fosSKF 38393Immediate-early gene transcription factorsIntestinal peptideReceptor antagonistReceptor agonistSecond messenger pathwaysCalcium channelsDifferentiated neuronsBrief stimulationImmediate early genesIEG expression
1992
Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons
Vaccarino F, Hayward M, Nestler E, Duman R, Tallman J. Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons. Brain Research 1992, 12: 233-241. PMID: 1347632, DOI: 10.1016/0169-328x(92)90089-t.Peer-Reviewed Original ResearchMeSH Keywords1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsAnimals, NewbornBlotting, NorthernCells, CulturedCerebral CortexCorpus StriatumDNA-Binding ProteinsEarly Growth Response Protein 1Gene Expression RegulationGenes, fosGenes, junGenes, RegulatorGlutamatesGlutamic AcidGlycineImmediate-Early ProteinsIsoquinolinesNeuronsPiperazinesProtein Kinase InhibitorsProto-OncogenesQuinoxalinesQuisqualic AcidRatsReceptors, AMPAReceptors, N-Methyl-D-AspartateReceptors, NeurotransmitterRNA, MessengerSulfonamidesTranscription FactorsConceptsProtein kinase C inhibitor HNGFI-A mRNAC-fosImmediate early genesPrimary culturesC-JunEarly genesGene mRNAN-methyl-D-aspartate receptor typeExcitatory amino acid receptor typesReceptor typesInhibitor HHydroxy-5-methylisoxazolepropionic acidExcitatory amino acid glutamateIEG expressionTransmembrane calcium influxDifferential inductionNMDA receptor channelsNMDA receptor activationAmino acid glutamateMRNAReceptor activationImmediate early gene mRNAsReceptor channelsCerebral cortex