Fig. 4. Alternative polyadenylation in schizophrenia affects synaptic pathways.

a, Pathway enrichment (odds-ratio y-axis) for transcripts subject to dAPA between ISCZ and HC in iNs (left) or adult postmortem PFC (right).

b, Enrichment of for transcripts subject to dAPA (between ISCZ and HC) in iNs (left) or adult PFC (right) in synapse related biological processes based on SYNGO.⁴⁶

c, Representative images from high content imaging (HCI) analysis of SYN1 (red), b3TUBB (green), and DAPI (white) ICC signal without (left) and with (right) neurite segmentation mask shown in iNs from HC and ISCZ. Scale bar indicates 50 μm.

d, Distribution of normalized SYN1 punctae density overlapping with neurites in iNs derived from HC and ISCZ donors at day 49. Density was assessed by HCI across n=10 HC and n=10 ISCZ iN samples across 66 wells in total and two independent differentiation batches. P-value indicates two-tailed significance level of linear mixed model based comparison between ISCZ and HC punctae density distributions.

e, Representative visualization of digital quantitative western blot for PSD-95 protein abundance and b3TUB across 10 HC and 10 ISCZ iN samples at day 49 with b3TUB loading control.

f, Distribution of normalized PSD-95 protein abundance levels in HC and ISCZ iNs at day 49 of differentiation using quantitative western blot based on the log₂ ratio of PSD95 and bTUBB signal intensity. P-value indicates two-tailed significance level of linear mixed model based comparison of n=28 (11 donors) HC and n=26 (14 donors) SCZ samples from three independent iN differentiation batches.