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 clonesCell 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 neuronsRiboTagCells
2018
THC 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
2017
THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons
Obiorah I, Muhammad H, Stafford K, Flaherty E, Brennand K. THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons. Complex Psychiatry 2017, 3: 73-84. PMID: 29230395, PMCID: PMC5701275, DOI: 10.1159/000477762.Peer-Reviewed Original ResearchTHC exposureHuman-induced pluripotent stem cellsGlutamate receptor gene expressionHuman stem cell-derived neuronsHiPSC-derived neuronsStem cell-derived neuronsΔ9-tetrahydrocannabinol exposureGlutamate receptor subunit genesCell-derived neuronsGenetic risk factorsReceptor gene expressionRisk factorsExcitatory neuronsHuman neuronsReceptor subunit genesBehavioral effectsNeuronsDisease vulnerabilityStem cellsPluripotent stem cellsExposureVariety of genotypesGene expressionExpressionSubunit gene
2016
Activity-Dependent Changes in Gene Expression in Schizophrenia Human-Induced Pluripotent Stem Cell Neurons
Roussos P, Guennewig B, Kaczorowski D, Barry G, Brennand K. Activity-Dependent Changes in Gene Expression in Schizophrenia Human-Induced Pluripotent Stem Cell Neurons. JAMA Psychiatry 2016, 73: 1180-1188. PMID: 27732689, PMCID: PMC5437975, DOI: 10.1001/jamapsychiatry.2016.2575.Peer-Reviewed Original ResearchConceptsGene coexpression analysisActivity-dependent changesGene expressionCandidate genesCoexpression analysisSchizophrenia candidate genesSpecific molecular functionsGenome-wide profilingPluripotent stem cell-derived neuronsGene expression differencesSchizophrenia-associated variantsStem cell-derived neuronsDifferential expression analysisNeuronal activity-dependent changesHuman-induced pluripotent stem cell-derived neuronsCell-derived neuronsHuman-induced pluripotent stem cellsPluripotent stem cell neuronsPluripotent stem cellsCommon molecular pathwaysSchizophrenia risk genesMolecular functionsGene networksEtiopathogenesis of schizophreniaExpression analysis
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 controlsMachineryProteinAbundance
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 cells