2024
Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease
Huang Y, Wang M, Ni H, Zhang J, Li A, Hu B, Junqueira Alves C, Wahane S, Rios de Anda M, Ho L, Li Y, Kang S, Neff R, Kostic A, Buxbaum J, Crary J, Brennand K, Zhang B, Zou H, Friedel R. Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease. Nature Neuroscience 2024, 27: 1489-1504. PMID: 38802590, PMCID: PMC11346591, DOI: 10.1038/s41593-024-01664-w.Peer-Reviewed Original ResearchPlexin-B1Alzheimer's diseaseGlial netsNetwork hub genesLate-onset ADPlaque-associated astrocytesPathophysiology of Alzheimer's diseaseMouse AD modelPlaque compactionNeuritic dystrophyHub genesGuidance receptorsTranscriptional changesAD modelAmyloid depositsAmyloidReducing neuroinflammationGlial cellsReactive astrocytesReceptor Plexin-B1Net activityGlial processesDeletionGenesCell distance
2023
The functional and evolutionary impacts of human-specific deletions in conserved elements
Xue J, Mackay-Smith A, Mouri K, Garcia M, Dong M, Akers J, Noble M, Li X, Lindblad-Toh K, Karlsson E, Noonan J, Capellini T, Brennand K, Tewhey R, Sabeti P, Reilly S, Andrews G, Armstrong J, Bianchi M, Birren B, Bredemeyer K, Breit A, Christmas M, Clawson H, Damas J, Di Palma F, Diekhans M, Dong M, Eizirik E, Fan K, Fanter C, Foley N, Forsberg-Nilsson K, Garcia C, Gatesy J, Gazal S, Genereux D, Goodman L, Grimshaw J, Halsey M, Harris A, Hickey G, Hiller M, Hindle A, Hubley R, Hughes G, Johnson J, Juan D, Kaplow I, Karlsson E, Keough K, Kirilenko B, Koepfli K, Korstian J, Kowalczyk A, Kozyrev S, Lawler A, Lawless C, Lehmann T, Levesque D, Lewin H, Li X, Lind A, Lindblad-Toh K, Mackay-Smith A, Marinescu V, Marques-Bonet T, Mason V, Meadows J, Meyer W, Moore J, Moreira L, Moreno-Santillan D, Morrill K, Muntané G, Murphy W, Navarro A, Nweeia M, Ortmann S, Osmanski A, Paten B, Paulat N, Pfenning A, Phan B, Pollard K, Pratt H, Ray D, Reilly S, Rosen J, Ruf I, Ryan L, Ryder O, Sabeti P, Schäffer D, Serres A, Shapiro B, Smit A, Springer M, Srinivasan C, Steiner C, Storer J, Sullivan K, Sullivan P, Sundström E, Supple M, Swofford R, Talbot J, Teeling E, Turner-Maier J, Valenzuela A, Wagner F, Wallerman O, Wang C, Wang J, Weng Z, Wilder A, Wirthlin M, Xue J, Zhang X. The functional and evolutionary impacts of human-specific deletions in conserved elements. Science 2023, 380: eabn2253. PMID: 37104592, PMCID: PMC10202372, DOI: 10.1126/science.abn2253.Peer-Reviewed Original ResearchConceptsHuman-specific deletionHuman phenotypic traitsParallel reporterEvolutionary impactDevelopmental genesPhenotypic traitsEvolutionary mechanismsGenomic sequencesNew traitsTranscriptomic datasetsSequence altersRegulatory functionsCell typesRegulatory activityRich resourceDeletionSynaptic functionTraitsBrain developmentGenesSpeciesReporterHumansSequenceExpression
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
2013
Mosaic Copy Number Variation in Human Neurons
McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T, Cowing-Zitron C, Shumilina S, Lasken RS, Vermeesch JR, Hall IM, Gage FH. Mosaic Copy Number Variation in Human Neurons. Science 2013, 342: 632-637. PMID: 24179226, PMCID: PMC3975283, DOI: 10.1126/science.1243472.Peer-Reviewed Original ResearchConceptsCopy number variationsHiPSC-derived neuronsSingle-cell genomic approachesNumber variationsDNA copy number variationsSingle-cell sequencingHuman neuronsLarge copy number variationsStem cell linesNeural progenitor cellsNovo copy-number variationsPluripotent stem cell lineAneuploid neuronsGenomic approachesDe novo copy-number variationsSubchromosomal copy number variationsAberrant genomesFrontal cortex neuronsLarge deletionsProgenitor cellsCell linesSubset of neuronsEuploid neuronsDeletionMultiple alterations