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Adult mouse cortical cell taxonomy revealed by single cell transcriptomics
Bosiljka Tasic1,2, Vilas Menon1,2, Thuc Nghi Nguyen1, Tae Kyung Kim1, Tim Jarsky1, Zizhen Yao1, Boaz Levi1, Lucas T Gray1, Staci A Sorensen1, Tim Dolbeare1, Darren Bertagnolli1, Jeff Goldy1, Nadiya Shapovalova1, Sheana Parry1, Changkyu Lee1, Kimberly Smith1, Amy Bernard1, Linda Madisen1, Susan M Sunkin1, Michael Hawrylycz1, Christof Koch1 & Hongkui Zeng1
Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructeda cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell typespecific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.
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area in adult (8-week-old) male mice. We selected the primary visual cortex (VISp or V1), which processes and transforms visual sensory information, and is one of the main models for understanding cortical computation and function18. To access both abundant and rare cell types in VISp, we selected a set of transgenic mouse lines in which Cre recombinase is expressed in specific subsets of cortical cells19
(Supplementary Table 1). Each Cre line was crossed to the Ai14 Cre reporter line, which expresses the fluorescent protein tdTomato (tdT) after Cre-mediated recombination (Supplementary Fig. 1a, Supplementary Table 2 and Online Methods). To label more specific cell populations, we combined Cre lines with Dre or Flp recombinase lines and intersectional reporter lines (Ai65 or Ai66; Supplementary Fig. 1a, Supplementary Table 2 and Online Methods). To isolate individual cells for transcriptional profiling, we sectioned fresh brains from adult transgenic male mice, microdissected the full cortical depth, combinations of sequential layers or individual layers (L1, 2/3, 4, 5 and 6) of VISp, and generated single-cell suspensions using a previously published procedure5 with some modifications (Fig. 1a, Supplementary Fig. 1b and Online Methods). We developed a robust procedure...