Fig. 6

AP-derived cINPCs exhibit elevated ER stress, which is rescued by the ryanodine receptor antagonist JTV-519. a, b Analysis of differential gene expression between the models did not identify a significant difference in expression of ER chaperones or ER stress genes in a, while b AP-derived cortical neuroids exhibited increased expression of the neural-enriched ryanodine receptor RYR3. RNA-seq data is derived from four biological replicate experiments (n = 4), which used one clonal line per model as described in the “Methods” section. Clones, replicates, and data values are in Additional file 5. c Expression of a Secreted ER Calcium Monitoring Protein Gaussia Luciferase stress sensor (SERCaMP-GLUC) in cINPCs demonstrated elevated ER stress in AP-derived cINPCs. d The use of the SERCaMP-GLUC reporter assay in the AP model demonstrated that this elevated ER stress phenotype could be suppressed by treatment with the ryanodine receptor antagonist JTV-519, but not with the chemical chaperones PBA and TUDCA or with another ryanodine receptor antagonist, dantrolene. Four independent biological replicate experiments (n = 4) were performed using two clonal lines for the AP and UM models and one clonal line for the UC-F and UC-M models. Clones, replicates, and data values are in Additional file 4. Plot shows the median value, calculated by using a Kruskal-Wallis non-parametric test as described in the Methods. P values: *P < 0.05, **P < 0.01, and ***P < 0.001