2017
Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network
McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T, Cortes-Ciriano I, Erwin JA, Fasching L, Flasch DA, Freed D, Ganz J, Jaffe AE, Kwan KY, Kwon M, Lodato MA, Mills RE, Paquola ACM, Rodin RE, Rosenbluh C, Sestan N, Sherman MA, Shin JH, Song S, Straub RE, Thorpe J, Weinberger DR, Urban AE, Zhou B, Gage FH, Lehner T, Senthil G, Walsh CA, Chess A, Courchesne E, Gleeson JG, Kidd JM, Park PJ, Pevsner J, Vaccarino FM, Barton A, Bekiranov S, Bohrson C, Burbulis I, Chronister W, Coppola G, Daily K, D’Gama A, Emery S, Frisbie T, Gao T, Gulyás-Kovács A, Haakenson M, Keil J, Kopera H, Lam M, Lee E, Marques-Bonet T, Mathern G, Moldovan J, Oetjens M, Omberg L, Peters M, Pochareddy S, Pramparo T, Ratan A, Sanavia T, Shi L, Skarica M, Wang J, Wang M, Wang Y, Wierman M, Wolpert M, Woodworth M, Zhao X, Zhou W. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science 2017, 356 PMID: 28450582, PMCID: PMC5558435, DOI: 10.1126/science.aal1641.Peer-Reviewed Original ResearchConceptsSomatic mutationsComplex genetic architectureStructural genomic variantsNeuronal genomeNeuronal transcriptomeGenetic architectureCell divisionCellular metabolismGenomic variantsLong life spanDNA damageComplex neuropsychiatric disorderCellular expansionNeuropsychiatric diseasesNeuropsychiatric disordersProgenitor cellsSomatic mosaicismIndividual neurodevelopmentSmall populationCell proliferationPopulation-based studyMutationsGermline variantsLife spanBrain developmentOne thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin
Abyzov A, Tomasini L, Zhou B, Vasmatzis N, Coppola G, Amenduni M, Pattni R, Wilson M, Gerstein M, Weissman S, Urban AE, Vaccarino FM. One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin. Genome Research 2017, 27: 512-523. PMID: 28235832, PMCID: PMC5378170, DOI: 10.1101/gr.215517.116.Peer-Reviewed Original ResearchConceptsSomatic mosaicismFibroblast cellsSingle-cell whole-genome amplificationAllele frequenciesNumber of SNVsNormal cell proliferationCell proliferationWhole genome amplificationStem cell linesPluripotent stem cell lineHealthy human tissuesDe novo variantsCancer mutationsHigh-resolution analysisMutational loadPCR experimentsSkin fibroblast cellsMutational signaturesHiPSC linesDe novoGenomeNovo variantsFibroblast populationsCell linesSomatic SNVs
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
2009
Fgfr1 Is Required for Cortical Regeneration and Repair after Perinatal Hypoxia
Fagel DM, Ganat Y, Cheng E, Silbereis J, Ohkubo Y, Ment LR, Vaccarino FM. Fgfr1 Is Required for Cortical Regeneration and Repair after Perinatal Hypoxia. Journal Of Neuroscience 2009, 29: 1202-1211. PMID: 19176828, PMCID: PMC2768410, DOI: 10.1523/jneurosci.4516-08.2009.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnalysis of VarianceAnimalsAnimals, NewbornBromodeoxyuridineCell ProliferationCerebral CortexCreatinineDNA-Binding ProteinsGlial Fibrillary Acidic ProteinHypoxiaMiceMice, Inbred C57BLMice, TransgenicNerve RegenerationNeurogenesisNeuronsOlfactory BulbParvalbuminsPhosphopyruvate HydrataseReceptor, Fibroblast Growth Factor, Type 1T-Box Domain ProteinsConceptsWild-type miceCortical neuronsOlfactory bulbSubventricular zoneChronic postnatal hypoxiaNeonatal hypoxic injuryPersistent behavioral deficitsExcitatory cortical neuronsSVZ cell proliferationCell proliferationPostnatal day 3Receptor 1 geneNormoxic miceOB neurogenesisReactive neurogenesisPerinatal hypoxiaPostnatal hypoxiaNeuronal recoveryFibroblast growth factor receptor 1 (FGFR1) geneHypoxic miceChronic hypoxiaGABAergic interneuronsHypoxic injuryResidual deficitsCortical regeneration
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
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
1997
Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of developing basal ganglia
Ding M, Robel L, James A, Eisenstat D, Leckman J, Rubenstein J, Vaccarino F. Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of developing basal ganglia. Journal Of Molecular Neuroscience 1997, 8: 93-113. PMID: 9188040, DOI: 10.1007/bf02736776.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody SpecificityAntisense Elements (Genetics)Basal GangliaCell DifferentiationCell DivisionCells, CulturedCytoskeletal ProteinsDNA-Binding ProteinsFemaleGene Expression Regulation, DevelopmentalGenes, HomeoboxHomeodomain ProteinsIn Situ HybridizationMicrotubule-Associated ProteinsNeuritesNeuronsPhenotypePregnancyRatsRhombencephalonRNA-Binding ProteinsTelencephalonTranscription FactorsConceptsGene productsNeuronal differentiationMicrotubule-associated protein MAP1BHomeodomain-containing genesDlx-2Homeobox genesNeuronal polarityCellular phenotypesNeuronal lineageProtein MAP1BPrimary culturesCellular localizationMitotic cycleGlial fibrillary acidic proteinGenesProteinCell proliferationDendrite outgrowthExpression of MAP2MAP2-positive dendritesNeuronal dendritesNeurofilament subunitsExpressionMAP2 expressionMRNA