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
2020
Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanismsCell 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 neuronsRiboTagCellsModeling the complex genetic architectures of brain disease
Fernando MB, Ahfeldt T, Brennand KJ. Modeling the complex genetic architectures of brain disease. Nature Genetics 2020, 52: 363-369. PMID: 32203467, PMCID: PMC7909729, DOI: 10.1038/s41588-020-0596-3.Peer-Reviewed Original ResearchConceptsGenetic architectureComplex genetic architectureFunctional validation studiesRelevant disease biologyIntersection of genomicsComplex genetic diseasesCombination of genesPluripotent stem cellsGene perturbationsIsogenic comparisonsMolecular mechanismsPhenotypic drug discoveryCell typesGenetic diseasesFunctional consequencesGenetic backgroundRisk variantsStem cellsCRISPRDisease biologyDrug discoveryRare variantsConfer riskGenetic diagnosisVariants
2017
Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity
Flaherty E, Deranieh R, Artimovich E, Lee I, Siegel A, Levy D, Nestor M, Brennand K. Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity. Schizophrenia 2017, 3: 35. PMID: 28970473, PMCID: PMC5624885, DOI: 10.1038/s41537-017-0033-5.Peer-Reviewed Original ResearchNeural progenitor cellsGene expressionGlobal gene expressionNeuronal gene expressionPluripotent stem cellsNeuronal activityFamily triosCell adhesion moleculeNeurexin familyHiPSC neuronsMolecular mechanismsDeletion displayAxon guidanceNeuronal developmentGenetic backgroundStem cellsProgenitor cellsDeletionMultiple neuropsychiatric conditionsHeterozygous intragenic deletionDendritic arborizationGenesAnimal studiesAdhesion moleculesNeuropsychiatric conditions
2016
Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease
Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand K, De Luca G, Crary J, Casaccia P, Buxbaum J, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B. Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease. Genome Medicine 2016, 8: 104. PMID: 27799057, PMCID: PMC5088659, DOI: 10.1186/s13073-016-0355-3.Peer-Reviewed Original ResearchConceptsGene expression changesCell type-specific marker genesExpression changesSingle-cell RNA-sequencing dataCo-expressed gene modulesLarge-scale gene expressionTranscriptomic network analysisCo-expression networkRNA-sequencing dataIntegrative network analysisNervous system developmentSelective regional vulnerabilityCritical molecular pathwaysActin cytoskeletonGenomic studiesGene modulesGenomic analysisGene expression abnormalitiesMarker genesMolecular basisGene expressionNetwork analysisMolecular mechanismsAxon guidanceMolecular pathwaysAltered proliferation and networks in neural cells derived from idiopathic autistic individuals
Marchetto M, Belinson H, Tian Y, Freitas B, Fu C, Vadodaria K, Beltrao-Braga P, Trujillo C, Mendes A, Padmanabhan K, Nunez Y, Ou J, Ghosh H, Wright R, Brennand K, Pierce K, Eichenfield L, Pramparo T, Eyler L, Barnes C, Courchesne E, Geschwind D, Gage F, Wynshaw-Boris A, Muotri A. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Molecular Psychiatry 2016, 22: 820-835. PMID: 27378147, PMCID: PMC5215991, DOI: 10.1038/mp.2016.95.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsInsulin growth factor-1Pluripotent stem cellsTranscriptional cascadeNeuronal networksAutism spectrum disorderGrowth factor-1Human cell modelsNormal brain sizeEarly brain overgrowthPotential cellular mechanismsMolecular mechanismsGenetic studiesClinical trialsIGF-1Therapeutic effectBrain pathologyAbnormal neurogenesisΒ-cateninCellular mechanismsStem cellsBrain overgrowthProgenitor cellsNeural cellsAltered proliferationChapter 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
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