2024
Massively parallel disruption of enhancers active in human neural stem cells
Geller E, Noble M, Morales M, Gockley J, Emera D, Uebbing S, Cotney J, Noonan J. Massively parallel disruption of enhancers active in human neural stem cells. Cell Reports 2024, 43: 113693. PMID: 38271204, PMCID: PMC11078116, DOI: 10.1016/j.celrep.2024.113693.Peer-Reviewed Original ResearchHuman neural stem cellsNeural stem cellsStem cellsProliferation phenotypeAssociated with neurodevelopmental disordersNeurodevelopmental disordersEnhanced disruptionHuman Accelerated RegionsNeural progenitor proliferationEffects of genetic variationHuman cortical evolutionProgenitor proliferationSelf-renewalNeural progenitorsProgenitor populationsCerebral cortexChromatin interactionsHuman cerebral cortexNeural progenitor populationsGene regulationRegulatory elementsConserved regionGene disruptionGenetic variationRegulatory relationships
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolution
2015
The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment
Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, Liu W, Klei L, Lei J, Yin J, Reilly SK, Tebbenkamp AT, Bichsel C, Pletikos M, Sestan N, Roeder K, State MW, Devlin B, Noonan JP. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nature Communications 2015, 6: 6404. PMID: 25752243, PMCID: PMC4355952, DOI: 10.1038/ncomms7404.Peer-Reviewed Original ResearchConceptsASD risk genesRisk genesRegulatory networksAncient gene regulatory networksHuman neural stem cellsLoss of CHD8Specific regulatory networksGene regulatory networksCo-expression networkAutism risk genesEmbryonic mouse cortexChromatin modifiersIdentification of recurrentChromodomain-HelicaseChd8 knockdownNeural stem cellsMouse neurodevelopmentCHD8Human brain developmentFunction mutationsGenesStem cellsHuman neurodevelopmentNovo lossBrain development