Extended Data Fig. 3: Comparisons of neocortical interneuron types across and within species.

a, Examples of correlation (Pearson’s r) in fold difference of expressed genes between pairs of MGE-derived and of nonMGE-derived interneuron types across pairs of species. Comparing within and then across species corrects for potential species-specific (for example, sequence-related) influences on RNA sampling, as well as for latent technical variables that might distinguish brains of different species. Genes in red have >3-fold expression difference in either cell type in each species pair, showing that the most extreme DEGs (largely consisting of known ‘markers’ of each type) tended to be consistent between species, despite modest correlations overall. Expression values obtained from n = 10,177 mouse and n = 63,096 marmoset cortical interneurons. b, Cortical interneuron t-SNE plots for each species (same data as Fig. 1c), coloured by individual replicate. c, Measure of inter-individual variability in gene expression (mu) in major interneuron types in mouse, marmoset and human. For each cell type, normalized gene expression levels (averaged across individual cells) are compared between pairs of individuals of the same species. Marmosets and mice both exhibited more modest inter-individual differences than humans did, which probably reflects the effects of life histories, environments and age at sampling, which are more uniform in a laboratory setting. Higher values indicate greater variability. Note that while the mice are isogenic, whole-genome sequencing of the marmosets revealed that they exhibited sequence variation comparable to humans. d, mu scores stratified by pLI gene scores. Human haplo-insufficient (high-pLI) genes tended to have lower expression variability than low-pLI genes in humans but not in marmosets or mice.