Chunk #15 — Results — Network analysis of gene expression of control and SZ hiPSC NPCs identifies perturbations in neuronal maturation and cellular adhesion
In all, 481 unique genes (134 upregulated and 347 downregulated) showed >1.30-fold expression changes between SZ and control hiPSC NPCs (P<0.05) after correcting for multiple comparisons (Supplementary Figures 4A and B; Supplementary Table 3). The SZ hiPSC NPC gene signature (GS) overlapped significantly (Bonferroni-corrected, P=2.4e–30, 4.9-fold) with our previously published SZ iPSC 6-week-old neuron GS,11 and the consistency of the directions of the differential expressions in SZ hiPSC NPC GS and SZ hiPSC 6-week-old neuron GS was more significant than the inconsistency. For example, the up- and downregulated gene sets in SZ hiPSC NPC GS highly overlapped their counterparts in SZ hiPSC 6-week-old neuron GS (Bonferroni-corrected, P<1.8e–10 (6.8-fold) and 1.6e–19 (8-fold), respectively), whereas the up- and downregulated gene sets in SZ hiPSC NPC GS were very insignificantly enriched in the down- and upregulated gene sets in SZ hiPSC 6-week-old neuron GS (Bonferroni-corrected, P=0.4 and 1, respectively). Much of the SZ 6-week-old neuron GS is conserved in SZ NPCs, suggesting that the molecular events contributing to SZ are established before neuronal differentiation.
