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 multi-cohort dissection of the schizophrenia transcriptome
Ruzicka W, Mohammadi S, Fullard J, Davila-Velderrain J, Subburaju S, Tso D, Hourihan M, Jiang S, Lee H, Bendl J, Voloudakis G, Haroutunian V, Hoffman G, Roussos P, Kellis M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, 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, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, 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, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, 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, 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, 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, Rozowsky J, Ruth M, 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, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, 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. Single-cell multi-cohort dissection of the schizophrenia transcriptome. Science 2024, 384: eadg5136. PMID: 38781388, DOI: 10.1126/science.adg5136.Peer-Reviewed Original ResearchConceptsGenetic risk factorsRisk factorsTranscriptional changesHeterogeneity of schizophreniaNeuronal cell statesSchizophrenia pathophysiologySingle-cell dissectionExcitatory neuronsEffective therapySchizophrenia transcriptomicsCortical cytoarchitectureSingle-cell atlasGenomic variantsCell groupsHuman prefrontal cortexMolecular pathwaysSchizophreniaTranscriptional alterationsTranscriptomic changesPrefrontal cortexCell statesAlterationsTherapyPathophysiologyDissectionA data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Huuki-Myers L, Spangler A, Eagles N, Montgomery K, Kwon S, Guo B, Grant-Peters M, Divecha H, Tippani M, Sriworarat C, Nguyen A, Ravichandran P, Tran M, Seyedian A, Hyde T, Kleinman J, Battle A, Page S, Ryten M, Hicks S, Martinowich K, Collado-Torres L, Maynard 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, 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. A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex. Science 2024, 384: eadh1938. PMID: 38781370, PMCID: PMC11398705, DOI: 10.1126/science.adh1938.Peer-Reviewed Original ResearchConceptsRNA sequencing dataCell type compositionGene expression platformSpatial transcriptomics technologiesAnterior-posterior axisCell-cell interactionsTranscriptome mapExpression platformHuman dorsolateral prefrontal cortexTranscriptomic technologiesSingle-cellCell typesPrefrontal cortexMolecular organizationDorsolateral prefrontal cortexHuman prefrontal cortex
2023
Lineage specific 3D genome structure in the adult human brain and neurodevelopmental changes in the chromatin interactome
Rahman S, Dong P, Apontes P, Fernando M, Kosoy R, Townsley K, Girdhar K, Bendl J, Shao Z, Misir R, Tsankova N, Kleopoulos S, Brennand K, Fullard J, Roussos P. Lineage specific 3D genome structure in the adult human brain and neurodevelopmental changes in the chromatin interactome. Nucleic Acids Research 2023, 51: 11142-11161. PMID: 37811875, PMCID: PMC10639075, DOI: 10.1093/nar/gkad798.Peer-Reviewed Original ResearchConceptsChromatin interactomeNeural developmentSpecific gene expressionEnhancer-promoter loopsDistinct cell typesGenome compartmentalizationRepressive compartmentGenome architectureFine-scale changesGenome structureChromatin loopsGWAS lociTAD boundariesTranscriptional inactivationActive promotersGene expressionInteractomeGenomeCell typesComplex organDisease mechanismsHuman brainAdult prefrontal cortexAdult human brainNeurodevelopmental processes
2021
Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor
Webb BD, Evans A, Naidich TP, Bird L, Parikh S, Garcia M, Henderson LB, Millan F, Si Y, Brennand KJ, Hung P, Rucker JC, Wheeler PG, Schadt EE. Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor. Human Mutation 2021, 42: 685-693. PMID: 33783914, PMCID: PMC8162891, DOI: 10.1002/humu.24201.Peer-Reviewed Original ResearchConceptsIntention tremorHead magnetic resonance imagingFunction variantsHypertrophic olivary degenerationCerebellar vermian atrophyMagnetic resonance imagingAtaxia syndromeWhole-exome sequencingVermian atrophyTranscription factor 1Olivary degenerationNervous systemResonance imagingMultiple abnormalitiesFactor 1POU4F1ProbandsSyndromeHypotoniaTremorClass 4De novoIndependent probandsAtrophyNewbornsCommon Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection
Dobrindt K, Hoagland DA, Seah C, Kassim B, O'Shea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Møller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports 2021, 16: 505-518. PMID: 33636110, PMCID: PMC7881728, DOI: 10.1016/j.stemcr.2021.02.010.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCOVID-19FemaleFurinGenetic Predisposition to DiseaseHost-Pathogen InteractionsHumansInduced Pluripotent Stem CellsMaleNeuronsPeptide HydrolasesPolymorphism, Single NucleotideSARS-CoV-2Vero CellsConceptsSARS-CoV-2Clinical complicationsSARS-CoV-2 infectionCommon genetic variationHigh-risk individualsHost genetic variantsSignificant interindividual variabilityNeuron infectionUnderlying comorbiditiesViral loadHealthy individualsViral infectionClinical heterogeneityVitro SusceptibilityEtiologic agentHost responseInterindividual variabilityDiscovery of drugsInfectionHost geneticsHuman induced pluripotent stem cellsSingle nucleotide polymorphismsAntibody repertoireMore diseasesComplications
2020
Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism
Breen MS, Browne A, Hoffman GE, Stathopoulos S, Brennand K, Buxbaum JD, Drapeau E. Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism. Molecular Autism 2020, 11: 53. PMID: 32560742, PMCID: PMC7304190, DOI: 10.1186/s13229-020-00355-0.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutistic DisorderChildChild, PreschoolChromosome DeletionChromosome DisordersChromosomes, Human, Pair 22FemaleGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsMaleNeural Stem CellsNeuronsReproducibility of ResultsWnt Signaling PathwayConceptsNeural progenitor cellsTranscriptional signatureGene co-expression network analysisHiPSC-NPCsCo-expression network analysisIndependent biological samplesHiPSC-derived neural cellsProgenitor cellsPostsynaptic density genesDistinct transcriptional signaturesGenetic risk lociHuman-induced pluripotent stem cellsPluripotent stem cellsPotassium channel activityProtein translationSpecific neurobiological pathwaysTranscriptional differencesEmbryonic developmentLoss of SHANK3Risk lociHiPSC neuronsMorphological phenotypesWnt pathwayGenesHiPSC clonesSex-Specific Role for the Long Non-coding RNA LINC00473 in Depression
Issler O, van der Zee YY, Ramakrishnan A, Wang J, Tan C, Loh YE, Purushothaman I, Walker DM, Lorsch ZS, Hamilton PJ, Peña CJ, Flaherty E, Hartley BJ, Torres-Berrío A, Parise EM, Kronman H, Duffy JE, Estill MS, Calipari ES, Labonté B, Neve RL, Tamminga CA, Brennand KJ, Dong Y, Shen L, Nestler EJ. Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression. Neuron 2020, 106: 912-926.e5. PMID: 32304628, PMCID: PMC7305959, DOI: 10.1016/j.neuron.2020.03.023.Peer-Reviewed Original ResearchConceptsSex-specific phenotypesLong non-coding RNAsNon-coding RNAsStress resilienceHuman neuron-like cellsRegulatory transcriptsSex-specific patternsSex-specific roleNeuron-like cellsGene expressionFemale miceLong NonViral-mediated gene transferGene transferLINC00473Prefrontal cortexSynaptic functionRate of menPhenotypeCommon disorderPFC neuronsDepressed femalesDepressed humansFemale depressionComplex regionA psychiatric disease-related circular RNA controls synaptic gene expression and cognition
Zimmerman AJ, Hafez AK, Amoah SK, Rodriguez BA, Dell’Orco M, Lozano E, Hartley BJ, Alural B, Lalonde J, Chander P, Webster MJ, Perlis RH, Brennand KJ, Haggarty SJ, Weick J, Perrone-Bizzozero N, Brigman JL, Mellios N. A psychiatric disease-related circular RNA controls synaptic gene expression and cognition. Molecular Psychiatry 2020, 25: 2712-2727. PMID: 31988434, PMCID: PMC7577899, DOI: 10.1038/s41380-020-0653-4.Peer-Reviewed Original ResearchConceptsSynaptic gene expressionCircular RNAsGene expressionAlternative mRNA transcriptsDisease-associated circRNAsHomolog 1Neuronal RNAMRNA transcriptsRNASynaptic expressionAge of onsetMammalian brainCircRNAsPotential involvementDorsolateral prefrontal cortexOrbitofrontal cortexBipolar disorderPrefrontal cortexKnockdownExpressionFrontal cortexSynaptic plasticityNeuronal culturesPsychiatric diseasesMouse orbitofrontal cortex
2019
Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development
Breen MS, Bierer LM, Daskalakis NP, Bader HN, Makotkine I, Chattopadhyay M, Xu C, Buxbaum Grice A, Tocheva AS, Flory JD, Buxbaum JD, Meaney MJ, Brennand K, Yehuda R. Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development. Translational Psychiatry 2019, 9: 201. PMID: 31434874, PMCID: PMC6704073, DOI: 10.1038/s41398-019-0539-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersConstitutive Androstane ReceptorDexamethasoneDose-Response Relationship, DrugGene ExpressionGene Expression ProfilingGene Regulatory NetworksGlucocorticoidsHumansLeukocytes, MononuclearMaleMiddle AgedStress Disorders, Post-TraumaticTranscription, GeneticVeteransYoung AdultConceptsPeripheral blood mononuclear cellsPost-traumatic stress disorderGlucocorticoid signalingCultured peripheral blood mononuclear cellsBlood immune cellsBlood mononuclear cellsTranscriptional responseConcentrations of dexamethasoneDifferential transcriptional changesGenome-wide gene expression profilingCombat-exposed veteransStress-responsive pathwaysMolecular responseClinical manifestationsInflammatory cytokinesDynamic transcriptional responseMononuclear cellsApoptosis-related pathwaysImmune cellsBaseline differencesDifferential transcriptional responsesDifferential molecular responsesGlucocorticoid stimulationNovel markerReliable marker
2018
Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder
McCarthy MJ, Wei H, Nievergelt CM, Stautland A, Maihofer AX, Welsh DK, Shilling P, Alda M, Alliey-Rodriguez N, Anand A, Andreasson OA, Balaraman Y, Berrettini WH, Bertram H, Brennand KJ, Calabrese JR, Calkin CV, Claasen A, Conroy C, Coryell WH, Craig DW, D’Arcangelo N, Demodena A, Djurovic S, Feeder S, Fisher C, Frazier N, Frye MA, Gage FH, Gao K, Garnham J, Gershon ES, Glazer K, Goes F, Goto T, Harrington G, Jakobsen P, Kamali M, Karberg E, Kelly M, Leckband SG, Lohoff F, McInnis MG, Mondimore F, Morken G, Nurnberger JI, Obral S, Oedegaard KJ, Ortiz A, Ritchey M, Ryan K, Schinagle M, Schoeyen H, Schwebel C, Shaw M, Shekhtman T, Slaney C, Stapp E, Szelinger S, Tarwater B, Zandi PP, Kelsoe JR. Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology 2018, 44: 620-628. PMID: 30487653, PMCID: PMC6333516, DOI: 10.1038/s41386-018-0273-8.Peer-Reviewed Original ResearchConceptsBipolar disorderEffects of lithiumMaintenance treatmentBD patientsCircadian rhythmMinority of patientsLithium maintenance treatmentMood stabilizer treatmentSerious mood disorderCircadian rhythm abnormalitiesCircadian rhythm parametersClinical responseCircadian rhythm functionLithium monotherapyClinical trialsMood disordersRhythm abnormalitiesMood symptomsPharmacological effectsPatientsEvening chronotypeStabilizer treatmentCommon genetic variationRhythm parametersMonotherapy
2017
Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Hoffman GE, Hartley BJ, Flaherty E, Ladran I, Gochman P, Ruderfer DM, Stahl EA, Rapoport J, Sklar P, Brennand KJ. Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains. Nature Communications 2017, 8: 2225. PMID: 29263384, PMCID: PMC5738408, DOI: 10.1038/s41467-017-02330-5.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, SurfaceAutopsyBrainCase-Control StudiesChildDNA Copy Number VariationsFemaleHumansInduced Pluripotent Stem CellsLinear ModelsMaleNanog Homeobox ProteinNestinNeural Stem CellsNeuronsOctamer Transcription Factor-3ProteoglycansRNA, MessengerSchizophreniaSequence Analysis, RNASOXB1 Transcription FactorsStage-Specific Embryonic AntigensSynapsinsTranscriptomeYoung AdultVariations in brain defects result from cellular mosaicism in the activation of heat shock signalling
Ishii S, Torii M, Son AI, Rajendraprasad M, Morozov YM, Kawasawa YI, Salzberg AC, Fujimoto M, Brennand K, Nakai A, Mezger V, Gage FH, Rakic P, Hashimoto-Torii K. Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling. Nature Communications 2017, 8: 15157. PMID: 28462912, PMCID: PMC5418582, DOI: 10.1038/ncomms15157.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBrainCell MovementEmbryo, MammalianEthanolFemaleGene Expression Regulation, DevelopmentalHeat Shock Transcription FactorsHumansHydrogen PeroxideInjections, IntraperitonealMaleMaternal ExposureMiceMice, TransgenicNeural Stem CellsNeuronsPhenotypePregnancyPrenatal Exposure Delayed EffectsPrimary Cell CultureSignal TransductionCommon 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
Altered WNT Signaling in Human Induced Pluripotent Stem Cell Neural Progenitor Cells Derived from Four Schizophrenia Patients
Topol A, Zhu S, Tran N, Simone A, Fang G, Brennand K. Altered WNT Signaling in Human Induced Pluripotent Stem Cell Neural Progenitor Cells Derived from Four Schizophrenia Patients. Biological Psychiatry 2015, 78: e29-e34. PMID: 25708228, PMCID: PMC4520784, DOI: 10.1016/j.biopsych.2014.12.028.Peer-Reviewed Original Research
2014
Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons
Hook V, Brennand K, Kim Y, Toneff T, Funkelstein L, Lee K, Ziegler M, Gage F. Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons. Stem Cell Reports 2014, 3: 531-538. PMID: 25358781, PMCID: PMC4223699, DOI: 10.1016/j.stemcr.2014.08.001.Peer-Reviewed Original ResearchConceptsHiPSC neuronsHuman-induced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsActivity-dependent secretionStem cell-derived neuronsCell-derived neuronsPositive neuronsCatecholamine levelsActivity-dependent mannerTyrosine hydroxylasePeptide neurotransmittersNeuronal culturesBrain disordersNeurotransmitter releaseChemical neurotransmissionKCl stimulationNeuronsNorepinephrineCatecholaminesElevated levelsNeurotransmitter secretionCatecholamine biosynthesisSchizophreniaDopamineNeurotransmittersPhenotypic 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 cells