Figure 5. Distinct cell-type-specific networks converge on FOXO1 targets in immature and mature glutamatergic neurons.

(A) Functional gene annotation (FUMA) identified sets of KOs with more specific shared function, beyond chromatin organization, and shared regulation by transcription factor and miRNAs. Network convergence across KOs based on functional annotation showed cell-type specificity and resolved networks with variable convergence and gene membership (i-ii). Convergent networks between targets of FOXO1 (PHF21A, SIN3A, and CHD2) were resolved in iGLUTs, but not NPCs and iGABAs. FOXO1 target convergent networks were unique in immature (B,i) and mature (C,i) iGLUTs. Central nodes in immature and mature iGLUTs included non-overlapping gene targets of psychiatric common and rare variants. The convergent network in immature iGLUTs was significantly enriched for immune networks related to IgA production (FDR<0.001) (B,ii) – network expansion using FunMap identified protein-protein connection between node genes that were nominally enriched for the regulation of stress response in immature iGLUTs (B,iii) (nom. P<0.01, adj. P=0.32). The convergent network in mature iGLUTs was significantly enriched 5-HT receptor mediated signaling (FDR<0.05) (C,ii) – network expansion identified a PPI network nominally enriched for cell communication (adj. P=0.066) and significantly enriched for positive regulation of cellular biosynthetic processes in mature iGLUTs (C,iii) (adj. P <=0.05).