2024
Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariants
2022
The three-dimensional landscape of cortical chromatin accessibility in Alzheimer’s disease
Bendl J, Hauberg M, Girdhar K, Im E, Vicari J, Rahman S, Fernando M, Townsley K, Dong P, Misir R, Kleopoulos S, Reach S, Apontes P, Zeng B, Zhang W, Voloudakis G, Brennand K, Nixon R, Haroutunian V, Hoffman G, Fullard J, Roussos P. The three-dimensional landscape of cortical chromatin accessibility in Alzheimer’s disease. Nature Neuroscience 2022, 25: 1366-1378. PMID: 36171428, PMCID: PMC9581463, DOI: 10.1038/s41593-022-01166-7.Peer-Reviewed Original ResearchConceptsOpen chromatin regionsCis-regulatory domainsChromatin accessibilitySpecific enhancer-promoter interactionsTranscription factor regulatory networksEnhancer-promoter interactionsATAC-seq librariesChromatin regionsLysosomal genesNonneuronal nucleiRegulatory networksThree-dimensional structureGenomeThree-dimensional landscapeRegulatory effectsAlzheimer's diseaseCommunity-based analysisUSF2GenesDysregulationRepertoireTFAD casesLandscapeDomainChromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
Farrelly L, Zheng S, Schrode N, Topol A, Bhanu N, Bastle R, Ramakrishnan A, Chan J, Cetin B, Flaherty E, Shen L, Gleason K, Tamminga C, Garcia B, Li H, Brennand K, Maze I. Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia. Nature Communications 2022, 13: 2195. PMID: 35459277, PMCID: PMC9033776, DOI: 10.1038/s41467-022-29922-0.Peer-Reviewed Original ResearchConceptsHistone posttranslational modificationsPosttranslational modificationsUnbiased proteomic approachPluripotent stem cellsPatient-derived neuronsH2A.Z acetylationChromatin profilingHyperacetylated histonesFamily proteinsProteomic approachProtein interactionsHistone acetylationTranscriptional abnormalitiesEpigenetic factorsExtraterminal (BET) proteinsSZ casesRisk variantsHuman neuronsStem cellsAberrant roleProtein inhibitionBona fideTreatment of schizophreniaPostmortem human brainCritical role
2019
Type I interferon response impairs differentiation potential of pluripotent stem cells
Eggenberger J, Blanco-Melo D, Panis M, Brennand KJ, tenOever BR. Type I interferon response impairs differentiation potential of pluripotent stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 1384-1393. PMID: 30606801, PMCID: PMC6347712, DOI: 10.1073/pnas.1812449116.Peer-Reviewed Original Research
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 targetsSubsetCells
2014
Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders
Hashimoto-Torii K, Torii M, Fujimoto M, Nakai A, Fatimy R, Mezger V, Ju MJ, Ishii S, Chao SH, Brennand KJ, Gage FH, Rakic P. Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders. Neuron 2014, 82: 560-572. PMID: 24726381, PMCID: PMC4051437, DOI: 10.1016/j.neuron.2014.03.002.Peer-Reviewed Original ResearchConceptsCerebral cortical cellsHuman neural progenitor cellsNeural progenitor cellsHeat shock factor 1Maternal seizuresSeizure susceptibilityPrenatal exposureNeuropsychiatric dysfunctionShock factor 1Neuronal responsesBrain cellsSchizophrenia patientsBrain disordersLate onsetMouse cortexStructural abnormalitiesNeuropsychiatric disordersHSF1 deficiencyExposure of embryosProgenitor cellsSubthreshold levelsFactor 1Induced pluripotent stem cellsEnvironmental insultsCortical cells
2008
Reprogramming of Pancreatic β Cells into Induced Pluripotent Stem Cells
Stadtfeld M, Brennand K, Hochedlinger K. Reprogramming of Pancreatic β Cells into Induced Pluripotent Stem Cells. Current Biology 2008, 18: 890-894. PMID: 18501604, PMCID: PMC2819222, DOI: 10.1016/j.cub.2008.05.010.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsPluripotent stem cellsCell typesIPS cellsStem cellsC-MycTranscription factors Oct4Rare cell typesInduced pluripotent stem cellsCertain cell typesAdult stem cellsInducible lentivirusVitro reprogrammingFactors OCT4Pluripotent cellsEctopic expressionGenetic proofPancreatic β-cellsGerm layersDifferentiated cellsChimeric animalsPluripotency markersDifferentiation stageBeta cellsPancreatic beta cells