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, 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.
Footnotes
This preprint has been updated from original biorXiv submission. The following are major changes: 1. Correction of GM12878 cell culturing and collection methods. GM12878 is a suspension cell line, not adherent. Thanks to Darren Cusanovich for identifying this error. 2. Addition of GM12878 data from Pliner, et al. (2018) to Supp Fig 4 and updates to some calculations. This better shows the high quality of current sci-ATAC-seq methods. Thanks to Jay Shendure and Darren Cusanovich for recommending this addition. 3. Updated analysis of Cusanovich, Hill, et al. (2018) data in Supp Fig 7 by changing the label metadata column selected. Thanks to Andrew Hill for recommending these higher-resolution labels. 4. Proper citation of Cusanovich, Hill et al. (2018), and discussion of the prior work in Drosophila in Cusanovich, Reddington, Garfield et al. (2018). Thanks to Jay Shendure for identifying these omissions. 5. Listing of R packages used for analysis.
