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 changesAlterationsEfficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang Y, Fasching L, Bae T, Tomasini L, Schreiner J, Szekely A, Fernandez T, Leckman J, Vaccarino F, Abyzov A. Efficient reconstruction of cell lineage trees for cell ancestry and cancer. Nucleic Acids Research 2023, 51: e57-e57. PMID: 37026484, PMCID: PMC10250207, DOI: 10.1093/nar/gkad254.Peer-Reviewed Original ResearchConceptsLineage treesCell ancestryCell lineage treesFirst cell divisionStem cell linesPluripotent stem cell lineLineage reconstructionInduced pluripotent stem cell lineCell divisionCancer progressionLineage representationCell linesMosaic mutationsHuman skin fibroblastsTreesMutationsAncestrySkin fibroblastsMultiple cellsGenomeLineagesZygotesLinesFibroblastsCells
2021
Comprehensive identification of somatic nucleotide variants in human brain tissue
Wang Y, Bae T, Thorpe J, Sherman MA, Jones AG, Cho S, Daily K, Dou Y, Ganz J, Galor A, Lobon I, Pattni R, Rosenbluh C, Tomasi S, Tomasini L, Yang X, Zhou B, Akbarian S, Ball LL, Bizzotto S, Emery SB, Doan R, Fasching L, Jang Y, Juan D, Lizano E, Luquette LJ, Moldovan JB, Narurkar R, Oetjens MT, Rodin RE, Sekar S, Shin JH, Soriano E, Straub RE, Zhou W, Chess A, Gleeson JG, Marquès-Bonet T, Park PJ, Peters MA, Pevsner J, Walsh CA, Weinberger DR, Vaccarino F, Moran J, Urban A, Kidd J, Mills R, Abyzov A. Comprehensive identification of somatic nucleotide variants in human brain tissue. Genome Biology 2021, 22: 92. PMID: 33781308, PMCID: PMC8006362, DOI: 10.1186/s13059-021-02285-3.Peer-Reviewed Original ResearchConceptsSomatic SNVsSomatic single nucleotide variantsWhole-genome sequencing dataSequencing dataBulk DNA samplesCell lineage treesSomatic mosaicismSingle nucleotide variantsLineage treesSomatic nucleotide variantsCellular processesDNA replicationHuman genomeSomatic tissuesDNA repairNucleotide variantsComprehensive identificationDNA samplesMosaic variantsNon-cancerous tissuesDNASingle individualMultiple replicatesHuman brain tissueVariantsEarly 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 Research
2020
Complex mosaic structural variations in human fetal brains
Sekar S, Tomasini L, Proukakis C, Bae T, Manlove L, Jang Y, Scuderi S, Zhou B, Kalyva M, Amiri A, Mariani J, Sedlazeck F, Urban AE, Vaccarino F, Abyzov A. Complex mosaic structural variations in human fetal brains. Genome Research 2020, 30: gr.262667.120. PMID: 33122304, PMCID: PMC7706730, DOI: 10.1101/gr.262667.120.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsCopy number variantsStructural variantsMegabase-scale copy number variantsHuman fetal brainFunctional consequencesMobile element insertionsSimilar functional consequencesFetal brainMosaic single-nucleotide variantsAdult brain neuronsStructural variationsPotential functional consequencesKilobase scaleDNA eventsGenomic fragmentDifferent chromosomesElement insertionsClonal approachHuman brain cellsFetal human brainNucleotide variantsReplication errorsHuman brainNumber variants
2017
Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T, Franjic D, Pletikos M, Pattni R, Chen BJ, Venturini E, Riley-Gillis B, Sestan N, Urban AE, Abyzov A, Vaccarino FM. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 2017, 359: 550-555. PMID: 29217587, PMCID: PMC6311130, DOI: 10.1126/science.aan8690.Peer-Reviewed Original ResearchConceptsSingle nucleotide variationsMutation rateCancer cell genomeClonal cell populationsCell genomeCell lineagesBackground mutagenesisHuman cellsMutational rateSomatic mosaicismSingle cellsOxidative damageGenomeMutagenesisCell populationsMutation spectrumNeurogenesisCellsHuman fetusesIndividual neuronsLineagesPregastrulationHuman brainBrainMutationsOne 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
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 ResearchModeling 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
2010
Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1
Swan LE, Tomasini L, Pirruccello M, Lunardi J, De Camilli P. Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 3511-3516. PMID: 20133602, PMCID: PMC2840420, DOI: 10.1073/pnas.0914658107.Peer-Reviewed Original Research
2009
A PH domain within OCRL bridges clathrin‐mediated membrane trafficking to phosphoinositide metabolism
Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin‐mediated membrane trafficking to phosphoinositide metabolism. The EMBO Journal 2009, 28: 1831-1842. PMID: 19536138, PMCID: PMC2711190, DOI: 10.1038/emboj.2009.155.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesClathrinCoated VesiclesEndocytosisHeLa CellsHumansModels, MolecularMolecular Sequence DataMutationNuclear Magnetic Resonance, BiomolecularPhosphatidylinositolsPhospholipidsPhosphoric Monoester HydrolasesProtein ConformationProtein Structure, TertiaryRatsSequence AlignmentConceptsPH domainNH2-terminal portionEndocytic clathrin-coated pitsClathrin-binding siteClathrin-coated pitsNMR structure determinationNH2-terminal regionCOOH-terminal regionClathrin-box motifsMembrane traffickingEvolutionary pressureSimilar proteinsINPP5BOCRLSpecialized functionsSequence dissimilarityLowe syndromePhosphoinositide metabolismDent's diseaseHeavy chainMutationsRecruitment efficiencyStructure determinationMetabolismDomain
2008
All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding
McCrea HJ, Paradise S, Tomasini L, Addis M, Melis MA, De Matteis MA, De Camilli P. All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. Biochemical And Biophysical Research Communications 2008, 369: 493-499. PMID: 18307981, PMCID: PMC2442618, DOI: 10.1016/j.bbrc.2008.02.067.Peer-Reviewed Original ResearchConceptsDisease-causing missense mutationsSpecific cellular sitesActive Rab5Endocytic pathwayProtein networkOCRLPatient mutationsAPPL1Missense mutationsLowe syndromeCellular sitesDisease phenotypeRab5Renal Fanconi syndromeMutationsDent's diseaseEndosomesDomainProteinBilateral cataractsNeonatal hypotoniaReabsorption defectFanconi syndromePhenotypeInositol