Extended Data Fig. 5: Meta-modules allow comparison between developing and adult cortical cell types.

a) Regardless of whether modules are derived from the developmental or the adult meta-atlas, adult subtypes typically harbor one or two strikingly specific modules while developmental cell types are represented by groups of modules with comparable specificity scores. Heat maps show module specificities of developmental modules on adult subtypes (top) and adult modules on developmental subtypes (bottom), with the average module specificity score and number of positively-scoring modules per subtype quantified in Fig. 3d. b) Evaluation of statistically significant overlap in gene composition across all developmental and adult modules. Heat map displays the p-values of the percent of genes in the indicated adult module (columns) that are shared in the indicated developmental module (rows). Statistical significance calculated using hypergeometric test. Though most adult modules share a significant overlap with at least one developmental module (top pie chart), the extent of overlap is overall low (bottom scatter plot). Adult modules overlap with developmental modules representing a variety of biological processes (bottom pie chart), most notably immune or synapse function. c) Developmental neuronal subtypes vary in their ability to be characterized by developmental vs adult meta-modules. Bar plots show the proportion of developmental vs adult modules among the 50 meta-modules with the highest specificity score within the indicated subtypes. Whereas upper layer excitatory neuronal subtypes are characterized primarily by adult modules, deep layer subtypes are represented largely by developmental modules. Among inhibitory neurons, CCK+ subtypes are represented equally by developmental and adult modules, whereas SST-expressing interneuron identity are driven largely by adult modules. d) Cell subtype-specificity of meta-modules diverge between development and adulthood. (left) Sankey plot tracks the 50 meta-modules with the highest specificity score for each adult subtype. For each of these modules, lines link their cell subtype-specificity in the adult meta-atlas to the developmental cell subtype for which this module displays the highest specificity. Percentages show the proportion of modules displaying the greatest specificity to the indicated cell subtype – for example, most modules (39.1%) are specific to the EN.CHRM3.GRIN2B subtypes in development, regardless of their cell subtype-specificity in the adult. (right) Analogous Sankey plot linking the 50 meta-modules with the highest specificity score for each developmental subtype and their cell subtype-specificity in the adult meta-atlas. e) Meta-modules specific to progenitors in development can mark distinct sets of cell types in the adult. Sankey plots show the top 50 modules (regardless of source) that are specific to either radial glia (left) or astrocyte/outer radial glia (right) in the developmental meta-atlas, and their subsequent cell type-specificities in the adult. Most of these modules (44–64%) are specific to astrocytes in the adult. But while there is some convergence, notably among adult glial and non-neuronal cells, developmental modules mark a distinct set of neuronal cells versus adult meta-modules.