Fig. 3: Transcriptional components represent intracellular coordination of gene expression programs with distinct developmental trajectories.

a, For each of approximately 50,000 single-cell RNA-seq samples, the weighted average expression of the negatively weighted genes of each AHBA component C1–C3 is plotted against that of the positively weighted genes (Methods). Samples are colored by cell type, demonstrating that genes positively and negatively weighted on C1–C3 have correlated expression within each major class of brain cells. Astro, astrocytes; Endo, endothelial cells; Micro, microglia; N-Ex, excitatory neurons; N-In, inhibitory neurons; Oligo, oligodendrocytes; OPC, oligodendrocyte precursor cell. Inset, a subset of samples from L2 VIP interneurons, illustrating that C1–C3 weighted genes were transcriptionally coupled even within a fine-grained, homogeneous group of cells. b, Cortical maps representing the regional scores of components C1–C3 for each of 11 regions with transcriptional data available in the BrainSpan cohort of adult brains (left) and C1–C3 component scores for the matching subset of regions in the AHBA (right). c, Scatter plots of matched regional C1–C3 scores from b, demonstrating that the three transcriptional components defined in the AHBA had consistent spatial expression in BrainSpan. d, Correlations between AHBA C1–C3 scores and BrainSpan C1–C3 scores (as in c) for each of three age-defined subsets of the BrainSpan dataset. C1 and C2 component scores were strongly correlated between datasets for all age subsets, whereas C3 component scores were strongly correlated between datasets only for the 18–40-year subset of BrainSpan. This indicates that C1 and C2 components were expressed in nearly adult forms from the earliest measured phases of brain development, whereas C3 was not expressed in adult form until after adolescence. e, Developmental trajectories of brain gene expression as a function of age (−0.5 years to 40 years; x axis, log scale) were estimated for each gene (Methods) and then averaged within each decile of gene weights for each of C1–C3; fitted lines are color-coded by decile. Genes weighted positively on C3 were most strongly expressed during adolescence, whereas genes weighted strongly on C1 or C2 were most expressed in the first 5 years of life. Dots above the x axis represent the postmortem ages of the donor brains used to compute the curves. RPKM, reads per kilobase per million mapped reads.