Abstract
Labeling and perturbation of specific cell types in multicellular systems has transformed our ability to understand them. The rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient access to these newly discovered types. To enable access to specific neural populations in the mouse cortex, we have collected single cell chromatin accessibility data from select cell types. We clustered the single cell data and mapped them to single cell transcriptomics to identify highly specific enhancers for cell subclasses. These enhancers, when cloned into AAVs and delivered to the brain by retro-orbital injections, enable transgene expression in specific cell subclasses throughout the mouse brain. This approach will enable functional investigation of cell types in the mouse cortex and beyond.
One sentence Summary Combining scATAC-seq and scRNA-seq identifies subclass-specific enhancers to label cells in mouse cortex at high resolution.
Author Contributions:
B.T., L.T.G., and T.D. designed the study; J.T., B.L,. and J.M. provided viral genome constructs and cloning protocols; G.L. performed cloning experiments. A.S.-C., T.N., and L.T.G. performed scATAC-seq experiments. B.K. performed electrophysiology experiments. A.C., S.Y., and M.M. performed viral packaging and purification. T.N. and M.M. performed retrograde injections. T.N. and E.S. performed stereotaxic injections. M.W. performed sectioning and IHC experiments. T.N. and E.G. performed additional validation experiments. N.D. managed tissue processing for RNA-seq experiments. K.S. managed RNA-seq experiments. Z.Y. and L.T.G. performed RNA-seq analysis. L.T.G. and A.S.-C. performed scATAC-seq analysis. H.Z. and E.L. lead the Cell Types Program at the Allen Institute. L.T.G. and B.T. wrote the manuscript, with input from all coauthors.
