2022
Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
Farrelly L, Zheng S, Schrode N, Topol A, Bhanu N, Bastle R, Ramakrishnan A, Chan J, Cetin B, Flaherty E, Shen L, Gleason K, Tamminga C, Garcia B, Li H, Brennand K, Maze I. Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia. Nature Communications 2022, 13: 2195. PMID: 35459277, PMCID: PMC9033776, DOI: 10.1038/s41467-022-29922-0.Peer-Reviewed Original ResearchConceptsHistone posttranslational modificationsPosttranslational modificationsUnbiased proteomic approachPluripotent stem cellsPatient-derived neuronsH2A.Z acetylationChromatin profilingHyperacetylated histonesFamily proteinsProteomic approachProtein interactionsHistone acetylationTranscriptional abnormalitiesEpigenetic factorsExtraterminal (BET) proteinsSZ casesRisk variantsHuman neuronsStem cellsAberrant roleProtein inhibitionBona fideTreatment of schizophreniaPostmortem human brainCritical role
2021
Using the dCas9-KRAB system to repress gene expression in hiPSC-derived NGN2 neurons
Li A, Cartwright S, Yu A, Ho SM, Schrode N, Deans PJM, Matos MR, Garcia MF, Townsley KG, Zhang B, Brennand KJ. Using the dCas9-KRAB system to repress gene expression in hiPSC-derived NGN2 neurons. STAR Protocols 2021, 2: 100580. PMID: 34151300, PMCID: PMC8188621, DOI: 10.1016/j.xpro.2021.100580.Peer-Reviewed Original ResearchMeSH KeywordsCRISPR-Cas SystemsGene Expression RegulationHumansInduced Pluripotent Stem CellsNerve Tissue ProteinsNeuronsTranscriptomeConceptsCRISPR inhibitionGene expressionDCas9-KRAB systemEndogenous gene expressionMultiple target genesGene repressionGene activationTarget genesGene manipulationFusion proteinComplete detailsPluripotent stemExpressionGlutamatergic neuronsRepressionGenesPhenotypicProteinStemNeuronsActivationBrain diseasesInhibition
2017
MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice
Mitchell A, Javidfar B, Pothula V, Ibi D, Shen E, Peter C, Bicks L, Fehr T, Jiang Y, Brennand K, Neve R, Gonzalez-Maeso J, Akbarian S. MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Molecular Psychiatry 2017, 23: 123-132. PMID: 28115742, PMCID: PMC5966823, DOI: 10.1038/mp.2016.254.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromatin ImmunoprecipitationCognition DisordersComputational BiologyDisease Models, AnimalEpigenomicsGene Expression RegulationGreen Fluorescent ProteinsHistonesMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsPolymorphism, Single NucleotideSchizophreniaTransduction, GeneticConceptsTherapeutic potentialPrefrontal projection neuronsNeuron-specific promoterUnexplored therapeutic potentialProjection neuronsDrug challengeDisease casesRelated disordersRisk architecturePrefrontal cortexSchizophreniaSingle nucleotide polymorphismsCognitive performancePsychiatric Genomics ConsortiumNeuronal genomeH3K4 hypermethylationRisk lociCognitive enhancement
2015
Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells
Ho S, Hartley B, Julia T, Beaumont M, Stafford K, Slesinger P, Brennand K. Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods 2015, 101: 113-124. PMID: 26626326, PMCID: PMC4860098, DOI: 10.1016/j.ymeth.2015.11.019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsNeural progenitor cellsHiPSC-derived neural progenitor cellsHigh-throughput drug screeningHiPSC neural progenitor cellsExogenous transcription factorsProgenitor cellsInduced pluripotent stem cellsPatient-specific platformPluripotent stem cellsPatient-derived neuronsSomatic reprogrammingTranscription factorsGenetic variationExcitatory neuronsDrug screeningNeurogenin 2Neuronal inductionFunctional neuronsThroughput drug screeningNeuronal phenotypeLentiviral transductionStem cellsStarting populationDisease etiology
2011
Concise Review: The Promise of Human Induced Pluripotent Stem Cell‐Based Studies of Schizophrenia
Brennand K, Gage F. Concise Review: The Promise of Human Induced Pluripotent Stem Cell‐Based Studies of Schizophrenia. Stem Cells 2011, 29: 1915-1922. PMID: 22009633, PMCID: PMC3381343, DOI: 10.1002/stem.762.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGenome-wide association studiesHuman induced pluripotent stem cellsHiPSC neuronsMolecular mechanismsStem cell-based studiesGene expression changesLive human neuronsInduced pluripotent stem cellsPluripotent stem cellsCommon single nucleotide polymorphismsRare copy number variantsCell-based studiesCopy number variantsSingle nucleotide polymorphismsExpression changesAssociation studiesCellular defectsHuman diseasesPost-mortem humanHeritable developmental disorderNumber variantsNucleotide polymorphismsHuman neuronsStem cellsGenesInvestigating synapse formation and function using human pluripotent stem cell-derived neurons
Kim J, O'Sullivan M, Sanchez C, Hwang M, Israel M, Brennand K, Deerinck T, Goldstein L, Gage F, Ellisman M, Ghosh A. Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 3005-3010. PMID: 21278334, PMCID: PMC3041068, DOI: 10.1073/pnas.1007753108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Adhesion Molecules, NeuronalCell DifferentiationChild Development Disorders, PervasiveDNA PrimersElectrophysiologyEmbryonic Stem CellsFluorescent Antibody TechniqueHEK293 CellsHumansInfant, NewbornMembrane ProteinsMicroscopy, ElectronMutationNerve Tissue ProteinsNeuronsPluripotent Stem CellsProsencephalonRatsReverse Transcriptase Polymerase Chain ReactionSynapsesTransfectionConceptsPluripotent stem cell-derived neuronsStem cell-derived neuronsCell-derived neuronsHuman pluripotent stem cell-derived neuronsStem cellsHuman embryonic stem cellsSynapse formationEmbryonic stem cellsSpecific cell typesHEK293T cellsPluripotent stem cellsHuman stem cellsAutism-associated mutationPresynaptic differentiationFrame deletionStem cell researchCell typesCell surfaceSynaptic differentiationVivo transplantationDifferentiationNLGN4Neuroligin-3CellsDrug development