2023
Lineage specific 3D genome structure in the adult human brain and neurodevelopmental changes in the chromatin interactome
Rahman S, Dong P, Apontes P, Fernando M, Kosoy R, Townsley K, Girdhar K, Bendl J, Shao Z, Misir R, Tsankova N, Kleopoulos S, Brennand K, Fullard J, Roussos P. Lineage specific 3D genome structure in the adult human brain and neurodevelopmental changes in the chromatin interactome. Nucleic Acids Research 2023, 51: 11142-11161. PMID: 37811875, PMCID: PMC10639075, DOI: 10.1093/nar/gkad798.Peer-Reviewed Original ResearchConceptsChromatin interactomeNeural developmentSpecific gene expressionEnhancer-promoter loopsDistinct cell typesGenome compartmentalizationRepressive compartmentGenome architectureFine-scale changesGenome structureChromatin loopsGWAS lociTAD boundariesTranscriptional inactivationActive promotersGene expressionInteractomeGenomeCell typesComplex organDisease mechanismsHuman brainAdult prefrontal cortexAdult human brainNeurodevelopmental processes
2022
Population-level variation in enhancer expression identifies disease mechanisms in the human brain
Dong P, Hoffman G, Apontes P, Bendl J, Rahman S, Fernando M, Zeng B, Vicari J, Zhang W, Girdhar K, Townsley K, Misir R, Brennand K, Haroutunian V, Voloudakis G, Fullard J, Roussos P. Population-level variation in enhancer expression identifies disease mechanisms in the human brain. Nature Genetics 2022, 54: 1493-1503. PMID: 36163279, PMCID: PMC9547946, DOI: 10.1038/s41588-022-01170-4.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociPopulation-level variationTranscriptome-wide association studyQuantitative trait lociSpecific transcriptomeTrait lociTrait heritabilitySpecific transcriptionEnhancer functionGenetic mechanismsTarget genesAssociation studiesDisease locusNeuropsychiatric diseasesRisk variantsGenesRobust expressionTranscriptomeFunctional interpretationDisease mechanismsEnhancerDiseased statesLociHuman brainBrain samples
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
Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms
Flaherty E, Brennand K. Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms. Brain Research 2015, 1655: 283-293. PMID: 26581337, PMCID: PMC4865445, DOI: 10.1016/j.brainres.2015.11.009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCopy number variationsIsogenic hiPSC linesRare variantsFull genetic architectureGenome editing technologyPluripotent stem cellsStrong heritable componentPatient-derived humanGenetic architectureEditing technologyHeritable componentBehavioral defectsNumber variationsNew therapeutic targetsHiPSC linesGenetic backgroundStem cellsCommon variantsFunctional contributionDisease mechanismsSingle variantMouse modelHigh penetranceHiPSCsTherapeutic target