2024
209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Seah C, Devarajan A, Jurczyszak D, Chakka A, Huckins L, Brennand K, Girgenti M. 209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling. Neurosurgery 2024, 70: 55-56. DOI: 10.1227/neu.0000000000002809_209.Peer-Reviewed Original ResearchIntracranial atherosclerotic stenosisIntracranial arteriesInterferon-inducible genesInterferon signalingPeripheral atherosclerosisCerebral atherosclerosisExpression of interferon-inducible genesGlial cellsSymptomatic intracranial atherosclerotic stenosisInduced pluripotent stem cellsPost-mortem brainsWorsened functional outcomesHuman induced pluripotent stem cellsUpregulation of interferon inducible genesCause of ischemic strokePluripotent stem cellsRisk of atherosclerosisLipid-rich plaquesRisk factor managementClinical outcomesPoor prognosisExcitatory neuronsIncreased morbidityHistopathological profileFunctional outcomes
2022
Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
Talvio K, Minkeviciene R, Townsley K, Achuta V, Huckins L, Corcoran P, Brennand K, Castrén M. Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome. Frontiers In Cell And Developmental Biology 2022, 10: 1034679. PMID: 36506088, PMCID: PMC9731341, DOI: 10.3389/fcell.2022.1034679.Peer-Reviewed Original ResearchInduced pluripotent stem cellsFragile X syndromeHuman induced pluripotent stem cellsNeural progenitorsX syndromeEarly gene expression changesGene expression changesPatient-derived induced pluripotent stem cellsTriplet repeat instabilityFunctional enrichment analysisHuman neural progenitorsPluripotent stem cellsRNA splicingPhenotypic variationIntellectual disability syndromeEnrichment analysisExpression changesRepeat instabilityMolecular mechanismsProtein resultsGrowth factor pathwaysInsulin-like growth factor (IGF) pathwayAltered expressionStem cellsTranscriptome
2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populationsCommon 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
Integrating 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
Modeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons
Chandrasekaran S, Rajarajan P, Akbarian S, Brennand K. Modeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem‐Cell‐Derived Neurons. 2018, 119-157. DOI: 10.1002/9781119283249.ch6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHuman induced pluripotent stem cellsInduced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsStem cell-derived neuronsZika virus epidemicPathophysiological mechanismsNeurological diseasesInduction protocolNeuropsychiatric diseasesCerebral organoidsTranslational benefitsVirus epidemicDrug testingDisease treatmentInduced pluripotent stem cellsDiseaseNeuronsStem cellsOptimization of differentiationPluripotent stem cellsSpecific subsetNeuroscience researchCulture dishesTransplantationBrain
2017
Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human Induced Pluripotent Stem Cells
Prytkova I, Brennand K. Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human Induced Pluripotent Stem Cells. Frontiers In Cellular Neuroscience 2017, 11: 360. PMID: 29217999, PMCID: PMC5703699, DOI: 10.3389/fncel.2017.00360.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInhibitory GABAergic neuronsAbnormal neuronal functionStem cellsPluripotent stem cellsGABAergic neuronsDopaminergic neuronsNetwork dysfunctionSZ pathologyDifficult disorderPatient-derived pluripotent stem cellsGlial culturesAnimal modelsNeuronal functionNetwork pathologyPatient-specific mannerHuman induced pluripotent stem cellsMolecular dysfunctionCo-culture techniqueInduced pluripotent stem cellsDysfunctionHigh rateDifferent cell typesNeuronsPathologyCell types
2016
Neural organoids for disease phenotyping, drug screening and developmental biology studies
Hartley B, Brennand K. Neural organoids for disease phenotyping, drug screening and developmental biology studies. Neurochemistry International 2016, 106: 85-93. PMID: 27744003, PMCID: PMC5389930, DOI: 10.1016/j.neuint.2016.10.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman induced pluripotent stem cellsNeural organoidsCell-extracellular matrix interactionsCell typesDevelopmental biology studiesSpecific physiological functionsCell-cell interactionsInduced pluripotent stem cellsNervous system cell typesCentral nervous system cell typesPluripotent stem cellsCell replacement therapyBiology studiesCurrent biomedical researchDifferentiation protocolsPhysiological functionsComplex tissuesMatrix interactionsNovel technological platformStem cellsDisease mechanismsSpatial organizationUnknown disease mechanismsToxicity assaysHeterogeneous tissues
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
2014
Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
Schadt E, Buchanan S, Brennand K, Merchant K. Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders. Frontiers In Pharmacology 2014, 5: 252. PMID: 25520658, PMCID: PMC4251289, DOI: 10.3389/fphar.2014.00252.Peer-Reviewed Original ResearchBiology approachNeurological disease pathwaysSpecific neural cell typesSystems biology approachPatient-derived hiPSCsDrug discoveryGeneration of hiPSCsInduced pluripotent stem cellsRepresentative neurological diseasesHuman induced pluripotent stem cellsNeural cell typesPluripotent stem cellsSingle geneGlobal epigeneticExpression studiesFrequent clinical failuresDrug screening strategiesNeurodegenerative diseases Alzheimer's diseaseHuman diseasesPsychiatric disorders schizophreniaCell typesCNS disordersHiPSC linesDisease pathwaysBiological networks
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 cellsGenes