To identify molecular specializations across cortical regions, we performed semi-supervised ICA on cells from frontal and posterior cortex (grouped together), analyzing each cell class separately. Glutamatergic neurons generated more regionally specialized ICs than GABAergic interneurons and non-neurons (Figure 5A), and exhibited subclusters with skewed regional abundances (Figure 5B–D). Selective markers for these cell subclusters confirmed their asymmetric distributions across the cortical mantle (Figure 5D and Figure S5). Glutamatergic neurons exhibited unusual regional specialization not only in subpopulation representation (subclusters), but in the precise gene expression pattern within each subpopulation: far more genes were differentially expressed when comparing regions within glutamatergic neuron as opposed to interneuron or non-neuronal subpopulations (Figure 5E). All these lines of evidence suggest that regional specializations are driven by glutamatergic neurons, consistent with theory from humans and other primates (Krienen et al., 2016).
