2024
Massively parallel characterization of regulatory elements in the developing human cortex
Deng C, Whalen S, Steyert M, Ziffra R, Przytycki P, Inoue F, Pereira D, Capauto D, Norton S, Vaccarino F, Pollen A, Nowakowski T, Ahituv N, Pollard K, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bhattacharya A, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clarke D, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Haroutunian V, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Hoffman G, Huang Y, Huuki-Myers L, Hwang A, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Khullar S, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Roussos P, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Sestan N, Seyfried N, Shao Z, Shedd N, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Massively parallel characterization of regulatory elements in the developing human cortex. Science 2024, 384: eadh0559. PMID: 38781390, DOI: 10.1126/science.adh0559.Peer-Reviewed Original ResearchConceptsGene regulatory elementsRegulatory elementsRegulation of enhancer activityCharacterization of regulatory elementsCis-regulatory activityNeuronal developmentPrimary cellsEnhanced activityGene regulationHuman neuronal developmentNucleotide changesEnhancer sequencesSequence basisUpstream regulatorComprehensive catalogHuman cellsDeveloping cortexSequenceVariantsOrganoidsCellsCerebral organoidsCortexHuman cortexNucleotideCharacterization 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
2023
Author Correction: 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. Author Correction: Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nature Neuroscience 2023, 26: 2035-2035. PMID: 37674007, DOI: 10.1038/s41593-023-01447-9.Peer-Reviewed Original ResearchModeling 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 changesAlterationsFUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation
Colantoni A, Capauto D, Alfano V, D’Ambra E, D’Uva S, Tartaglia G, Morlando M. FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation. International Journal Of Molecular Sciences 2023, 24: 3181. PMID: 36834591, PMCID: PMC9968238, DOI: 10.3390/ijms24043181.Peer-Reviewed Original ResearchConceptsRNA metabolismHuman motor neuronsNuclear/cytoplasmic partitioningNon-canonical splicing eventsAspects of RNASubset of circRNAsCytoplasmic partitioningCytoplasmic circRNAsSplicing eventsMutant proteinsCircular RNAsMotor neuronsAlu repeatsExon compositionCircRNAsProteinRNAMutationsFUS mutationsKey eventsFUSPreferential bindingP525L mutationMetabolismPivotal role
2022
A multifunctional locus controls motor neuron differentiation through short and long noncoding RNAs
Carvelli A, Setti A, Desideri F, Galfrè SG, Biscarini S, Santini T, Colantoni A, Peruzzi G, Marzi MJ, Capauto D, Di Angelantonio S, Ballarino M, Nicassio F, Laneve P, Bozzoni I. A multifunctional locus controls motor neuron differentiation through short and long noncoding RNAs. The EMBO Journal 2022, 41: embj2021108918. PMID: 35698802, PMCID: PMC9251839, DOI: 10.15252/embj.2021108918.Peer-Reviewed Original ResearchConceptsMN differentiationPost-transcriptional roleSingle-cell sequencingMotor neuron differentiationPostmitotic motor neuronsTranscriptional unitsMESC differentiationTranscription factorsCRISPR/Transcriptional levelMiR-466iNeuron differentiationNeuronal differentiationFunctional relevanceMotor neuronsMiR-384-5pDifferentiationSeries of eventsProliferation-related factorsAdditional layerMutantsMiRNAsLncRNAsLociRNA
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 tissuesTranscriptomicsLineagesBiology
2019
Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders
D’Ambra E, Capauto D, Morlando M. Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders. International Journal Of Molecular Sciences 2019, 20: 5477. PMID: 31689888, PMCID: PMC6862314, DOI: 10.3390/ijms20215477.Peer-Reviewed Original ResearchConceptsCircular RNAsRegulatory non-coding RNAsNon-coding RNAsImportant regulatory functionsNeuronal specificationPathological conditionsCircRNAs expressionGene expressionCircRNAsNeuronal developmentRegulatory functionsExact functionRegulatory roleDifferent tissuesSynaptic plasticity inductionRNANervous systemNeurodegenerative diseasesNeurodegenerative disordersInnovative therapeutic approachesDynamic modulationRecent studiesExpressionDistinctive classCurrent advances
2018
A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons
Capauto D, Colantoni A, Lu L, Santini T, Peruzzi G, Biscarini S, Morlando M, Shneider NA, Caffarelli E, Laneve P, Bozzoni I. A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons. Molecular Neurobiology 2018, 55: 7635-7651. PMID: 29430619, PMCID: PMC6132778, DOI: 10.1007/s12035-018-0884-4.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisMotor neuronsFUS mutationsMouse embryonic stem cellsPathogenesis of ALSMiRNA-dependent regulationCorresponding mRNA targetsNeuron-specific RNATypes of RNAEmbryonic stem cellsCross talkGlutamate α-aminoIsoxazole propionic acidDisease-associated mutationsMolecular cross talkDisturbance of Ca2Juvenile-onset formMiRNA repressionRegulatory circuitryTranscriptome profilingMRNA targetsMultifunctional proteinLong RNAsMN degenerationExcitatory neurotransmissionCharacterization of the lncRNA transcriptome in mESC-derived motor neurons: Implications for FUS-ALS
Biscarini S, Capauto D, Peruzzi G, Lu L, Colantoni A, Santini T, Shneider NA, Caffarelli E, Laneve P, Bozzoni I. Characterization of the lncRNA transcriptome in mESC-derived motor neurons: Implications for FUS-ALS. Stem Cell Research 2018, 27: 172-179. PMID: 29449089, DOI: 10.1016/j.scr.2018.01.037.Peer-Reviewed Original ResearchConceptsLong non-coding transcriptomeMouse motor neuronsAmyotrophic lateral sclerosisNon-coding transcriptomeMotor neuronsSevere amyotrophic lateral sclerosisAberrant RNA metabolismLong non-coding RNAsStem cellsEmbryonic stem cellsNon-coding RNAsInduced pluripotent stem cellsNervous system developmentPluripotent stem cellsRNA metabolismLncRNA transcriptomeDifferentiation systemLateral sclerosisTDP-43TranscriptomeFUS-ALSCandidate lncRNAsCrucial playersCausative mutationsEssential role
2017
FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Errichelli L, Dini Modigliani S, Laneve P, Colantoni A, Legnini I, Capauto D, Rosa A, De Santis R, Scarfò R, Peruzzi G, Lu L, Caffarelli E, Shneider NA, Morlando M, Bozzoni I. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nature Communications 2017, 8: 14741. PMID: 28358055, PMCID: PMC5379105, DOI: 10.1038/ncomms14741.Peer-Reviewed Original ResearchConceptsMouse motor neuronsCircRNA biogenesisRNA-binding protein FUSEmbryonic stem cell-derived motor neuronsCircular RNA productionRNA biosynthetic processesCircular RNA expressionStem cell-derived motor neuronsCell-derived motor neuronsAmyotrophic lateral sclerosisMost circRNAsFUS mutantsSplicing junctionsProtein FUSSplicing reactionBiosynthetic processesRNA productionToxic gainCircRNAsMotor neuronsBiogenesisRNA expressionFunction activityNuclear levelsFUSDrosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration
Laneve P, Piacentini L, Casale AM, Capauto D, Gioia U, Cappucci U, Di Carlo V, Bozzoni I, Di Micco P, Morea V, Di Franco CA, Caffarelli E. Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration. Scientific Reports 2017, 7: 41559. PMID: 28139767, PMCID: PMC5282483, DOI: 10.1038/srep41559.Peer-Reviewed Original ResearchConceptsEukaryotic RNA metabolismDrosophila nervous systemTDP-43-mediated neurodegenerationImportant biological processesNovel family memberUnique biochemical featuresEssential endoribonucleaseRibosome biogenesisDrosophila viabilityRNA metabolismPositive regulatorFunctional characterisationBiosynthetic enzymesRibonuclease familyGene productsBiological processesMolecular levelNervous system activityBiochemical featuresCholinergic circuitsPhenotypeViral replicationNervous systemImmature phenotypeFamily members
2015
DOF AFFECTING GERMINATION 2 is a positive regulator of light-mediated seed germination and is repressed by DOF AFFECTING GERMINATION 1
Santopolo S, Boccaccini A, Lorrai R, Ruta V, Capauto D, Minutello E, Serino G, Costantino P, Vittorioso P. DOF AFFECTING GERMINATION 2 is a positive regulator of light-mediated seed germination and is repressed by DOF AFFECTING GERMINATION 1. BMC Plant Biology 2015, 15: 72. PMID: 25850831, PMCID: PMC4355143, DOI: 10.1186/s12870-015-0453-1.Peer-Reviewed Original ResearchConceptsSeed germination processPositive regulatorSeed germinationGermination processSeed germination phenotypesChromatin immuno-precipitation analysisImmuno-precipitation analysisGERMINATION 1Mutant seedsGermination phenotypePhytochrome BMaster repressorGibberellin biosynthesisGermination capabilityGermination potentialGerminationRepressorMutantsSeedsOpposite rolesRegulatorEnvironmental factorsDAG2ExpressionRed light
2014
Independent and interactive effects of DOF affecting germination 1 (DAG1) and the Della proteins GA insensitive (GAI) and Repressor of ga1-3(RGA) in embryo development and seed germination
Boccaccini A, Santopolo S, Capauto D, Lorrai R, Minutello E, Belcram K, Palauqui JC, Costantino P, Vittorioso P. Independent and interactive effects of DOF affecting germination 1 (DAG1) and the Della proteins GA insensitive (GAI) and Repressor of ga1-3(RGA) in embryo development and seed germination. BMC Plant Biology 2014, 14: 200. PMID: 25064446, PMCID: PMC4222566, DOI: 10.1186/s12870-014-0200-z.Peer-Reviewed Original ResearchConceptsGA INSENSITIVESeed germinationEmbryo developmentDouble mutantGai-t6GERMINATION 1Mutant seedsGa1-3Germination pathwaySingle mutantsRepressorUnexpected involvementMutantsDistinct rolesGerminationGermination propertiesIndependent branchInteractive effectsGERMINATION1DAG1DormancyGenesSeedsPathwayInactivationThe DOF Protein DAG1 and the DELLA Protein GAI Cooperate in Negatively Regulating the AtGA3ox1 Gene
Boccaccini A, Santopolo S, Capauto D, Lorrai R, Minutello E, Serino G, Costantino P, Vittorioso P. The DOF Protein DAG1 and the DELLA Protein GAI Cooperate in Negatively Regulating the AtGA3ox1 Gene. Molecular Plant 2014, 7: 1486-1489. PMID: 24719470, DOI: 10.1093/mp/ssu046.Peer-Reviewed Original Research