Featured Publications
Modelling schizophrenia using human induced pluripotent stem cells
Brennand K, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage F. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473: 221-225. PMID: 21490598, PMCID: PMC3392969, DOI: 10.1038/nature09915.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntipsychotic AgentsCell DifferentiationCells, CulturedCellular ReprogrammingChildDisks Large Homolog 4 ProteinFemaleFibroblastsGene Expression ProfilingGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsLoxapineMaleMembrane ProteinsModels, BiologicalNeuritesNeuronsPhenotypePluripotent Stem CellsReceptors, GlutamateSchizophreniaYoung Adult
2023
Multi-omic profiling of the developing human cerebral cortex at the single-cell level
Zhu K, Bendl J, Rahman S, Vicari J, Coleman C, Clarence T, Latouche O, Tsankova N, Li A, Brennand K, Lee D, Yuan G, Fullard J, Roussos P. Multi-omic profiling of the developing human cerebral cortex at the single-cell level. Science Advances 2023, 9: eadg3754. PMID: 37824614, PMCID: PMC10569714, DOI: 10.1126/sciadv.adg3754.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsChromatin accessibilityGene expressionPseudotime trajectory analysisNeuronal lineage commitmentMulti-omics profilingSingle-cell levelSpecific genetic lociDevelopmental time pointsChromatin structureType-specific domainsLineage determinationCellular complexityLineage commitmentNeuropsychiatric traitsComplex regulationGenetic lociSpatiotemporal activityDynamic changesCritical roleExpressionSpatiotemporal alterationsCell compositionCritical stageNeuropsychiatric diseases
2019
Leveraging Human Induced Pluripotent Stem Cell–Based Models Provides Biological Context to Genome-wide Association Study Findings
Brennand KJ. Leveraging Human Induced Pluripotent Stem Cell–Based Models Provides Biological Context to Genome-wide Association Study Findings. Biological Psychiatry 2019, 85: 532-533. PMID: 30871689, DOI: 10.1016/j.biopsych.2019.01.021.Peer-Reviewed Original ResearchType I interferon response impairs differentiation potential of pluripotent stem cells
Eggenberger J, Blanco-Melo D, Panis M, Brennand KJ, tenOever BR. Type I interferon response impairs differentiation potential of pluripotent stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 1384-1393. PMID: 30606801, PMCID: PMC6347712, DOI: 10.1073/pnas.1812449116.Peer-Reviewed Original Research
2018
New considerations for hiPSC-based models of neuropsychiatric disorders
Hoffman GE, Schrode N, Flaherty E, Brennand KJ. New considerations for hiPSC-based models of neuropsychiatric disorders. Molecular Psychiatry 2018, 24: 49-66. PMID: 29483625, PMCID: PMC6109625, DOI: 10.1038/s41380-018-0029-1.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationHumansInduced Pluripotent Stem CellsMental DisordersModels, BiologicalNeuronsPhenotypeReproducibility of ResultsConceptsHuman-induced pluripotent stem cellsCell type compositionComplex genetic diseasesPluripotent stem cellsComplex genetic disorderField of geneticsCell biologistsBiological convergenceLevel phenotypesAdvanced geneticsCRISPR technologyHuman diseasesPsychiatric genomicsGenetic diseasesStem cellsNeural cellsCommon variantsGeneticsGenetic disordersBiological considerationsCritical insightsCellsGenomicsRecent advancesBiologists
2017
Evaluating Synthetic Activation and Repression of Neuropsychiatric-Related Genes in hiPSC-Derived NPCs, Neurons, and Astrocytes
Ho S, Hartley B, Flaherty E, Rajarajan P, Abdelaal R, Obiorah I, Barretto N, Muhammad H, Phatnani H, Akbarian S, Brennand K. Evaluating Synthetic Activation and Repression of Neuropsychiatric-Related Genes in hiPSC-Derived NPCs, Neurons, and Astrocytes. Stem Cell Reports 2017, 9: 615-628. PMID: 28757163, PMCID: PMC5550013, DOI: 10.1016/j.stemcr.2017.06.012.Peer-Reviewed Original ResearchConceptsSynthetic activationRisk genesCell typesModulation of transcriptionNeuropsychiatric risk genesCommon single nucleotide variantsCas9 fusion proteinsEndogenous expression levelsNeural cell typesPluripotent stem cell-derived neural progenitor cellsRare copy number variationsCopy number variationsSingle nucleotide variantsNeural progenitor cellsGene functionFunctional annotationGenetic studiesGenesRisk variantsProgenitor cellsExpression levelsTranscriptionRepressionPositional effectsProteinAn Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells
Julia T, Wang M, Pimenova A, Bowles K, Hartley B, Lacin E, Machlovi S, Abdelaal R, Karch C, Phatnani H, Slesinger P, Zhang B, Goate A, Brennand K. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells. Stem Cell Reports 2017, 9: 600-614. PMID: 28757165, PMCID: PMC5550034, DOI: 10.1016/j.stemcr.2017.06.018.Peer-Reviewed Original ResearchCommon developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS)
Narla S, Lee Y, Benson C, Sarder P, Brennand K, Stachowiak E, Stachowiak M. Common developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS). Schizophrenia Research 2017, 185: 17-32. PMID: 28094170, PMCID: PMC5507209, DOI: 10.1016/j.schres.2016.12.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell DifferentiationCells, CulturedFemaleGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenomeGenomicsHumansInduced Pluripotent Stem CellsMaleMicroRNAsModels, BiologicalMutationReceptor, Fibroblast Growth Factor, Type 1Receptor, Notch1SchizophreniaSignal TransductionTranscriptomeYoung AdultConceptsMRNA networkMajor developmental pathwaysIntegrative nuclear FGFR1MiRNA-mRNA networkHuman gene promotersCommon developmental genomesMiRNA genesMiRNA transcriptomeGene networksUpregulated genesGene promoterNuclear FGFR1Genomic etiologyGene dysregulationDisease ontogenyNuclear formGlobal dysregulationDevelopmental pathwaysGenesNeuron formationDistinct pathwaysConcerted actionPotential therapeutic targetTranscriptomeGenome
2015
Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients
Topol A, English J, Flaherty E, Rajarajan P, Hartley B, Gupta S, Desland F, Zhu S, Goff T, Friedman L, Rapoport J, Felsenfeld D, Cagney G, Mackay-Sim A, Savas J, Aronow B, Fang G, Zhang B, Cotter D, Brennand K. Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients. Translational Psychiatry 2015, 5: e662-e662. PMID: 26485546, PMCID: PMC4930118, DOI: 10.1038/tp.2015.118.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCells, CulturedHumansInduced Pluripotent Stem CellsNeural Stem CellsNeuronsProsencephalonSchizophreniaConceptsHiPSC neural progenitor cellsNeural progenitor cellsNovel post-transcriptional mechanismProtein synthesisGlobal protein translationElongation factor proteinGlobal protein synthesisPost-transcriptional mechanismsProgenitor cellsHuman-induced pluripotent stem cellsPluripotent stem cellsMass spectrometry evidenceTranslation machineryTranslation initiationProtein translationEpigenetic factorsFactor proteinStem cellsProtein levelsTotal protein levelsCellsUnaffected controlsMachineryProteinAbundanceA guide to generating and using hiPSC derived NPCs for the study of neurological diseases.
Topol A, Tran N, Brennand K. A guide to generating and using hiPSC derived NPCs for the study of neurological diseases. Journal Of Visualized Experiments 2015, e52495. PMID: 25742222, PMCID: PMC4354663, DOI: 10.3791/52495.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCytological TechniquesHumansInduced Pluripotent Stem CellsNervous System DiseasesNeural Stem CellsConceptsNeural progenitor cellsHiPSC neural progenitor cellsRapid genetic screeningPluripotent stem cellsCellular phenotypesDevelopmental eventsMolecular consequencesGene expressionNeurological diseasesFunctional neuronsStem cellsProgenitor cellsOnset of symptomsMolecular factorsFurther differentiationPost-mortem studiesDisease initiationGenetic screeningOxidative stressSymptom onsetDisease progressionHealthy controlsDiseaseCellsPatientsDopaminergic differentiation of schizophrenia hiPSCs
Hartley B, Tran N, Ladran I, Reggio K, Brennand K. Dopaminergic differentiation of schizophrenia hiPSCs. Molecular Psychiatry 2015, 20: 549-550. PMID: 25623947, PMCID: PMC4500053, DOI: 10.1038/mp.2014.194.Peer-Reviewed Original Research
2014
Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia
Brennand K, Savas J, Kim Y, Tran N, Simone A, Hashimoto-Torii K, Beaumont K, Kim H, Topol A, Ladran I, Abdelrahim M, Matikainen-Ankney B, Chao S, Mrksich M, Rakic P, Fang G, Zhang B, Yates J, Gage F. Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Molecular Psychiatry 2014, 20: 361-368. PMID: 24686136, PMCID: PMC4182344, DOI: 10.1038/mp.2014.22.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntipsychotic AgentsCell DifferentiationCell MovementCells, CulturedFemaleGene ExpressionHumansMaleMiceMice, Inbred C57BLMice, TransgenicMitochondriaNeural Cell Adhesion MoleculesNeural Stem CellsOxidative StressPhenotypePluripotent Stem CellsProsencephalonProteomicsReactive Oxygen SpeciesSchizophreniaYoung AdultConceptsHiPSC neural progenitor cellsNeural progenitor cellsHuman-induced pluripotent stem cellsHiPSC-derived neuronsGene expressionGene expression comparisonsStable isotope labelingProteomic mass spectrometry analysisAbnormal gene expressionPluripotent stem cellsOxidative stressCytoskeletal remodelingMass spectrometry analysisCellular phenotypesExpression comparisonsDevelopmental mechanismsIsotope labelingPhenotypic differencesBrainSpan AtlasDisease predispositionAmino acidsScalable assayNPC phenotypeStem cellsProgenitor cellsModeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells
Yu D, Di Giorgio F, Yao J, Marchetto M, Brennand K, Wright R, Mei A, Mchenry L, Lisuk D, Grasmick J, Silberman P, Silberman G, Jappelli R, Gage F. Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells. Stem Cell Reports 2014, 2: 295-310. PMID: 24672753, PMCID: PMC3964286, DOI: 10.1016/j.stemcr.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsCell DifferentiationDentate GyrusElectrophysiological PhenomenaEmbryoid BodiesGene ExpressionGenes, ReporterHippocampusHomeodomain ProteinsHumansNerve NetNeural Stem CellsNeurogenesisNeuronsNeurotransmitter AgentsPluripotent Stem CellsPyramidal CellsSchizophreniaTumor Suppressor ProteinsConceptsHippocampal neurogenesisDentate gyrusHippocampal dentate gyrusDG granule neuronsStem cellsPluripotent stem cellsSpontaneous neurotransmitter releaseNeuronal network maturationPatient-derived humanHuman pluripotent stem cellsDifferentiation paradigmNeuronal activityGranule neuronsBrain regionsNeurotransmitter releaseNeurodevelopmental aspectsLineage-specific cellsNeurogenesisNeuronsNetwork maturationReduced levelsPersonalized medicineHuman diseasesCellsDrug screening
2013
Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells
Brennand K, Landek-Salgado M, Sawa A. Modeling Heterogeneous Patients With a Clinical Diagnosis of Schizophrenia With Induced Pluripotent Stem Cells. Biological Psychiatry 2013, 75: 936-944. PMID: 24331955, PMCID: PMC4022707, DOI: 10.1016/j.biopsych.2013.10.025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCell DifferentiationHumansInduced Pluripotent Stem CellsModels, NeurologicalNeuronsSchizophreniaSignal TransductionConceptsCommon clinical manifestationsSmall patient cohortPathology of schizophreniaStem cellsPluripotent stem cellsComplex genetic conditionClinical manifestationsPatient cohortClinical etiologyHuman neuronsAnimal modelsClinical heterogeneityHeterogeneous patientsClinical diagnosisSchizophreniaGenetic conditionsMental conditionPatientsGenetic variantsBiological mechanismsClinical constraintsRare genetic variantsCellsCohortEtiologyNeural stem and progenitor cells in health and disease
Ladran I, Tran N, Topol A, Brennand K. Neural stem and progenitor cells in health and disease. WIREs Mechanisms Of Disease 2013, 5: 701-715. PMID: 24068527, PMCID: PMC4160040, DOI: 10.1002/wsbm.1239.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAstrocytesCell DifferentiationHumansModels, NeurologicalNervous System DiseasesNeural Stem CellsNeuronsOligodendroglia
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 cellsGenesBrief Report: Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines
Woods N, Parker A, Moraghebi R, Lutz M, Firth A, Brennand K, Berggren W, Raya A, Belmonte J, Gage F, Verma I. Brief Report: Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines. Stem Cells 2011, 29: 1158-1164. PMID: 21544903, PMCID: PMC3254148, DOI: 10.1002/stem.657.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsMicePluripotent Stem CellsConceptsEmbryonic stem cellsHuman embryonic stem cellsHematopoietic stem cellsHematopoietic progenitorsStem cellsDifferentiation protocolsDefinitive hematopoietic stem cellsHuman pluripotent stem cell linesGeneration of precursorsMultipotent hematopoietic progenitorsIPSC linesStem cell linesPrimitive hematopoietic cellsPluripotent stem cellsPluripotent stem cell lineExtra-cellular matrix componentsEmbryonic developmentHematopoietic progenitor cellsDifferent human embryonic stem cellHematopoietic lineagesDifferentiation culturesHematopoietic potentialCellular matrix componentsNovel factorHematopoietic cellsInvestigating 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
2010
High-Efficient Generation of Induced Pluripotent Stem Cells from Human Astrocytes
Ruiz S, Brennand K, Panopoulos A, Herrerías A, Gage F, Izpisua-Belmonte J. High-Efficient Generation of Induced Pluripotent Stem Cells from Human Astrocytes. PLOS ONE 2010, 5: e15526. PMID: 21170306, PMCID: PMC3000364, DOI: 10.1371/journal.pone.0015526.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsHuman somatic cell typesEmbryoid body generationHuman embryonic stem cellsEmbryonic germ layersEmbryonic stem cellsStem cellsInduced pluripotent stem cellsTeratoma formationRegenerative medicineSomatic cell typesPluripotent markersReprogramming efficiencyHuman somatic cellsHiPS cellsHigh-efficient generationGerm layersAutologous cellsEfficiencySomatic cellsSimilar efficiencyPluripotencyNeural cell typesCell typesLayer
2009
Slow and steady is the key to β‐cell replication
Brennand K, Melton D. Slow and steady is the key to β‐cell replication. Journal Of Cellular And Molecular Medicine 2009, 13: 472-487. PMID: 19379145, PMCID: PMC2820566, DOI: 10.1111/j.1582-4934.2008.00635.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAgingAnimalsBone Marrow CellsCell DifferentiationCell DivisionHumansInsulin-Secreting CellsStem Cells