Fig. 4

Impaired glutamatergic signaling and neuronal immaturity in SEV lines. (A) GO enrichment analysis of downregulated DEGs at the early stage of differentiation in SEV versus HC and SEV versus MILD comparisons. (B) GO enrichment analysis of downregulated DEGs at the late stage of differentiation in SEV versus HC and SEV versus MILD comparisons. (C) Gene set enrichment analysis (GSEA) confirms negative enrichment of glutamatergic signaling-related terms in SEV versus HC and SEV versus MILD comparisons. (D and E) Expression of genes encoding for AMPA receptor subunits GRIA1 and GRIA2 across differentiation stages, showing increased GRIA1 and reduced GRIA2 expression in SEV neurons compared to HC and MILD lines. Data are presented as mean ± S.E.M. of 6 biological replicates for controls and 3 biological replicates for patients. (F) GRIA1/GRIA2 ratio in neurons at early and late stages of differentiation.