Fig. 1: AAV vectors elicit transduction-dependent transcriptional alterations in hiPSC-derived neurons and astrocytes.

Quantification of vector transduction efficiency by FACS analysis of GFP expression (A) and genome copy numbers (B) on hiPSC-derived neurons and astrocytes harvested 48 h post-transduction. Data are shown as mean between independent experiments (n = 3 for neurons, n = 3 for astrocytes transduced with AAV9, AAV5, Spk100 and UT; n = 2 for astrocytes transduced with AAV1, AAV2 and AAV6). C, D Heatmaps representing the level of differentially expressed genes (DEGs) in fold compared to untransduced (UT) samples. Each column constitutes one biological replicate. Heatmaps showing the enriched GSEA terms in hiPSC-derived neurons (E) and astrocytes (F) against the Hallmark gene set (Molecular Signatures Database). Each column represents the average between n = 3 biological replicates for all conditions except astrocytes UT (n = 4). GSEA was performed on logFC fold changes in gene expression in transduced samples compared to UT controls using Kolmogorov-Smirnov test with FDR for multiple test correction (NES, normalized enrichment score; *, adjusted P < 0.05; **, adjusted P < 0.01; ***, adjusted P < 0.01). Heatmaps showing the top upregulated and downregulated genes in hiPSC-derived neurons (G) and astrocytes (H) and the pathways they are associated with according to the Hallmark gene set. Source data are provided as a Source Data file.