Fig. 4: Genes with increased expression in highly connected nodes are enriched for subplate neurons and astrocytes.

A Enrichment of hub\({{\boldsymbol{+}}}\) genes in developmental cell lineages (bold) and cell subtypes in each post-mitotic tissue zone. Significant enrichments (p < 0.05 uncorr.) are highlighted with black outlines. B Total (log-normalised) expression of network hub\({{\boldsymbol{+}}}\) genes in each of 709,372 cells derived from brain tissue sampled across the human lifespan displayed using UMAP. Inset: territories for major cell classifications. C UMAP projections of neuronal and D glial cell populations (top), overlaid with developmental pseudotime trajectories. Differentiated subplate neurons, layer 5/6 IT neurons, and astrocyte territories are highlighted with red and yellow, respectively (top row). Plots are coloured by total gene expression of hub\({{\boldsymbol{+}}}\) genes (top) and developmental time (middle). Bottom row: scatterplots show the relationship between hub\({{\boldsymbol{+}}}\) gene expression and cell maturation for each population. E Association between node degree and average expression (Z-scored) of hub\({{\boldsymbol{+}}}\) genes expressed by subplate neurons (hub\({{\boldsymbol{+}}}\)_SP). F Average hub\({{\boldsymbol{+}}}\)_SP expression displayed on the µBrain cortical atlas (lateral and medial surfaces). Additional enrichment analyses are shown in (G) and (H). G Developmental enrichment of hub\({{\boldsymbol{+}}}\) genes across different ages in the BrainSpan RNA-seq dataset. Bold outlines indicate p < 0.05. H Enrichment in hub\({{\boldsymbol{+}}}\) genes of SNPs associated with different adult brain phenotypes^65,111, neurodevelopmental disorders of early (ASD)¹²⁰ and later (SCZ)¹²¹ onset and cross-disorder behavioural factors (F1: mood disorders and F2: psychopathology)¹²² (black circles indicate p < 0.05 uncorr.).