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
2024
Single-cell genomics and regulatory networks for 388 human brains
Emani P, Liu J, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee C, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken T, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard J, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman G, Huang A, Jiang Y, Jin T, Jorstad N, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran J, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan A, Riesenmy T, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini K, Wamsley B, Wang G, Xia Y, Xiao S, Yang A, Zheng S, Gandal M, Lee D, Lein E, Roussos P, Sestan N, Weng Z, White K, Won H, Girgenti M, Zhang J, Wang D, Geschwind D, Gerstein M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Brennand K, Capauto D, Champagne F, Chatzinakos C, Chen H, Cheng L, Chess A, Chien J, 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, Duong D, Eagles N, Edelstein J, Galani K, Girdhar K, Goes F, Greenleaf W, Guo H, Guo Q, Hadas Y, Hallmayer J, Han X, Haroutunian V, He C, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hyde T, Iatrou A, Inoue F, Jajoo A, Jiang L, Jin P, Jops C, Jourdon A, Kellis M, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Li J, Li M, Lin X, Liu S, Liu C, Loupe J, Lu D, Ma L, Mariani J, Martinowich K, Maynard K, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Mukamel E, Nairn A, Nemeroff C, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Pinto D, Pochareddy S, Pollard K, Pollen A, Przytycki P, Purmann C, Qin Z, Qu P, Raj T, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, 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, Wang T, Wang S, Wang Y, Wei Y, Weimer A, Weinberger D, Wen C, Whalen S, Willsey A, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang Y, Ziffra R, Zeier Z, Zintel T. Single-cell genomics and regulatory networks for 388 human brains. Science 2024, 384: eadi5199. PMID: 38781369, PMCID: PMC11365579, DOI: 10.1126/science.adi5199.Peer-Reviewed Original ResearchConceptsSingle-cell genomicsSingle-cell expression quantitative trait locusExpression quantitative trait lociDrug targetsQuantitative trait lociPopulation-level variationSingle-cell expressionCell typesDisease-risk genesTrait lociGene familyRegulatory networksGene expressionCell-typeMultiomics datasetsSingle-nucleiGenomeGenesCellular changesHeterogeneous tissuesExpressionCellsChromatinLociMultiomicsMassively 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 cortexNucleotide
2020
Pluripotent Stem Cells May Unlock How Genetic Variants Result in Mental Disorders
Powell S, Yu A, Katz C, Brennand K. Pluripotent Stem Cells May Unlock How Genetic Variants Result in Mental Disorders. Psychiatric News 2020, 55 DOI: 10.1176/appi.pn.2020.7b14.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models
Gregory JA, Hoelzli E, Abdelaal R, Braine C, Cuevas M, Halpern M, Barretto N, Schrode N, Akbalik G, Kang K, Cheng E, Bowles K, Lotz S, Goderie S, Karch CM, Temple S, Goate A, Brennand KJ, Phatnani H. Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models. Cells 2020, 9: 1406. PMID: 32516938, PMCID: PMC7349756, DOI: 10.3390/cells9061406.Peer-Reviewed Original ResearchConceptsCell type-restricted expressionDisease-associated interactionsGene expression profilingHiPSC-derived motor neuronsHuman-induced pluripotent stem cellsPluripotent stem cellsCell-type specific perturbationsImmortalized cell linesRibosomal proteinsGenomic studiesExpression profilingMolecular mechanismsOff-target RNAMouse tissuesCell typesStem cellsPrimary mouse astrocytesExperimental replicatesCell linesMixed speciesMouse astrocytesExpressionMotor neuronsRiboTagCellsIntegrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems
Rehbach K, Fernando MB, Brennand KJ. Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems. Journal Of Neuroscience 2020, 40: 1176-1185. PMID: 32024766, PMCID: PMC7002154, DOI: 10.1523/jneurosci.0518-19.2019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsMajor brain cell typesDual Perspectives CompanionBrain cell typesNeuronal maturityPsychiatric disordersHuman neuronsDisease riskStudy designBrain organoidsIntradonor variabilityDisease modelsHuman neurodevelopmentInduced pluripotent stem cellsNeural differentiationDiseaseStem cellsCell typesPluripotent stem cellsHuman diseasesEfficient neural differentiationInduction strategyPatient-specific cellsDisease modelingCells
2018
Expression-based drug screening of neural progenitor cells from individuals with schizophrenia
Readhead B, Hartley BJ, Eastwood BJ, Collier DA, Evans D, Farias R, He C, Hoffman G, Sklar P, Dudley JT, Schadt EE, Savić R, Brennand KJ. Expression-based drug screening of neural progenitor cells from individuals with schizophrenia. Nature Communications 2018, 9: 4412. PMID: 30356048, PMCID: PMC6200740, DOI: 10.1038/s41467-018-06515-4.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsHiPSC neural progenitor cellsCell typesCancer cell linesGene expression differencesProgenitor cellsDisease-associated genesPatient-specific platformPluripotent stem cellsTranscriptional responseExpression differencesTranscriptional signatureTranscriptomic signaturesStem cellsCell linesDependent mannerDrug discoveryDrug screeningCellsNeuropsychiatric disordersSchizophreniaBest treatmentDrugsDiscoveryGenesTHC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders
Guennewig B, Bitar M, Obiorah I, Hanks J, O’Brien E, Kaczorowski DC, Hurd YL, Roussos P, Brennand KJ, Barry G. THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Translational Psychiatry 2018, 8: 89. PMID: 29691375, PMCID: PMC5915454, DOI: 10.1038/s41398-018-0137-3.Peer-Reviewed Original ResearchConceptsHuman-induced pluripotent stem cellsPluripotent stem cellsHuman iPSC neuronsTranscriptional responseTranscriptomic analysisRNA transcriptomic analysisHuman neural cellsIPSC-neuronsMolecular pathwaysNeuropsychiatric disordersStem cellsNeural cellsDiagnosis-specific differencesGenesTHC exposureNeuronal depolarizationTHC administrationChronic exposureCannabis useNeuronsΔ9-tetrahydrocannabinolStrong associationSignificant alterationsCellsDynamic changesNew 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 ResearchConceptsHuman-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
2016
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells
Topol A, Zhu S, Hartley B, English J, Hauberg M, Tran N, Rittenhouse C, Simone A, Ruderfer D, Johnson J, Readhead B, Hadas Y, Gochman P, Wang Y, Shah H, Cagney G, Rapoport J, Gage F, Dudley J, Sklar P, Mattheisen M, Cotter D, Fang G, Brennand K. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells. Cell Reports 2016, 15: 1024-1036. PMID: 27117414, PMCID: PMC4856588, DOI: 10.1016/j.celrep.2016.03.090.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsControl neural progenitor cellsMiR-9 targetsProgenitor cellsSubset of patientsMiR-9Levels/activitiesMiR-9 expressionSchizophrenia patientsMicroRNA-9Migration deficitsDisease riskNeural migrationAberrant levelsAberrant migrationPatientsMiRNA-9SchizophreniaMigration-associated genesRNA sequencingSZ riskRiskIndirect targetsSubsetCellsChapter 23 hiPSC Models Relevant to Schizophrenia
Hartley B, Hadas Y, Brennand K. Chapter 23 hiPSC Models Relevant to Schizophrenia. Techniques In The Behavioral And Neural Sciences 2016, 23: 391-406. DOI: 10.1016/b978-0-12-800981-9.00023-7.ChaptersPluripotent stem cellsStem cellsPutative causal genesSpecific cellular phenotypesInduced pluripotent stem cellsGenomic lociTranscriptome sequencingRegulatory networksCausal genesCellular phenotypesGenetic manipulationMolecular mechanismsGenetic insultsFull complementPatient cellsEfficient derivationDisease initiationWealth of informationEnvironmental factorsRisk allelesCellsHuman brain tissueModel RelevantGross levelEtiology of schizophrenia
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 ResearchConceptsHiPSC 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 controlsMachineryProteinAbundanceStem cells in gels
Brennand K. Stem cells in gels. Science Translational Medicine 2015, 7 DOI: 10.1126/scitranslmed.aac5089.Commentaries, Editorials and LettersA 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 ResearchConceptsNeural 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 controlsDiseaseCellsPatients
2014
Modeling 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 StatementsConceptsCommon 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 Statements
2011
Modeling psychiatric disorders through reprogramming
Brennand K, Gage F. Modeling psychiatric disorders through reprogramming. Disease Models & Mechanisms 2011, 5: 26-32. PMID: 21954066, PMCID: PMC3255540, DOI: 10.1242/dmm.008268.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInduced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises
Marchetto M, Brennand K, Boyer L, Gage F. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Human Molecular Genetics 2011, 20: r109-r115. PMID: 21828073, PMCID: PMC4447776, DOI: 10.1093/hmg/ddr336.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInvestigating 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