Fig. 6: Several ASD risk factors share impaired IPC production and non-brain-like alternative isoform switches, which can be improved by ZMYND11.

a Schematic outlining Class I mutant lines and cortical differentiation. b PCA of RNA-seq on Class I mutant and isogenic control cortical NSCs (n = 11 for Class I mutants, n = 4 for isogenic controls). c Gene ontology analysis on upregulated genes in Class I mutant NSCs using biological processes. d Overlap of DAS events prediction from HISAT2-rMATS, STAR-rMATS and AltAnalyze. e Scatter plot of PSI difference between isogenic control and Class I mutants (x axis) & brain tissues and non-brain tissues (y axis). f Sashimi plots for MEAF6 exon 6 and L1CAM exon 3 from high-confidence DAS events in Class I mutant NSCs. Numbers in Sashimi plots indicate average PSI values. g Semiquantitative PCR of L1CAM exon 3 on both Class I mutant and Class II mutant NSCs and quantification (mean ± SEM, n = 3). h Schematic outlining ZMYND11 overexpression strategy during Class I mutant differentiation. i Flow cytometry analysis for FLAG expression in dox-treated Class I mutant monolayer culture at day 16 (left) with quantification (right, 200 ng/ml, mean ± SEM, n = 4). j Quantification of flow cytometry analysis for TBR2 (left) and TBR1 (right) on FLAG+ populations at day 16 relative to FLAG- population (mean ± SEM, n = 4). Statistics in (c): over-representation analysis with P.adjust values by Benjamini-Hochberg method. Statistics in (e): linear regression with correlation coefficient calculated using Pearson method. Statistics in (j): unpaired two-tailed t test. ns P  >  0.05, *P < 0.05; **P < 0.01. P values in (j): TBR2 + % for ASH1L, P = 0.0042; for DEAF1, P = 0.2700; for ASXL3, P = 0.0456; for CUL3, P = 0.0998; for KDM5B, P = 0.0094. TBR1 + % for ASH1L, P = 0.0303; for DEAF1, P = 0.1519; for ASXL3, P = 0.0013; for CUL3, P = 0.1848; for KDM5B, P = 0.0338. Source data are provided as a Source Data file.