biostudies-literatureGraybuck LTNIDA NIH HHSNIMH NIH HHSNational Institutes of Health1449-1464.e13https://www.ebi.ac.uk/biostudies/studies/S-EPMC8610077biostudies-literatureUnknown109(9)Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned into recombinant adeno-associated viruses (AAVs) and delivered to the brain, these enhancers drive transgene expression in specific cortical cell subclasses. We extensively characterized several enhancer AAVs to show that they label different projection neuron subclasses as well as a homologous neuron subclass in human cortical slices. We also show how coupling enhancer viruses expressing recombinases to a newly generated transgenic mouseNeuronEnhancer viruses for combinatorial cell-subclass-specific labeling.PMC8610077RF1 MH114126RF1 MH121274R01 DA036909Levi BPSunkin SMKalmbach BLenz GHGraybuck LTGoldy JMortrud MSiverts LABendrick JLSzelenyi ERTrader CWay SWYao ZGradinaru VLarsen RLein ETasic BEsposito LMorin ENguyen TNCetin AHWalker MGarren Evan Velthoven CTJZhou TYao STing JTBalaram PChiang MSmith KMich JKSedeno-Cortes AEDaigle TLZeng HGore BBKim TKDee NfalseEnhancer viruses for combinatorial cell-subclass-specific labeling.Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned into recombinant adeno-associated viruses (AAVs) and delivered to the brain, these enhancers drive transgene expression in specific cortical cell subclasses. We extensively characterized several enhancer AAVs to show that they label different projection neuron subclasses as well as a homologous neuron subclass in human cortical slices. We also show how coupling enhancer viruses expressing recombinases to a newly generated transgenic mouse2021-01-01T00:00:00Z2021 May2026-05-30T20:53:50.717Z2025-04-04T10:01:43.509ZS-EPMC86100773378908310.1016/j.neuron.2021.03.011