Fig. 5: AKAP8 regulates EMT in a cell state-specific manner through alternative splicing.

a Volcano plots showing differential alternative splicing events identified upon knockdown of AKAP8 in HMLE/Twist-ER untreated epithelial cells (EPI, top panel) and in tamoxifen-induced HMLE/Twist-ER mesenchymal cells (MES, bottom panel). Significant alternative splicing events (FDR < 0.05 and |∆PSI| > 0.1) were colored as green and red dots if AKAP8 knockdown resulted in skipping or inclusion, respectively. PSI: Percent Splice In. b Violin plot of differential alternative splicing distribution identified upon knockdown of AKAP8 in epithelial cells (top panel) and mesenchymal cells (bottom panel) grouped by alternative splicing types. A3SS: Alternative 3’ Splice Site; A5SS: Alternative 5’ Splice Site; MXE: Mutually Exclusive Exon; RI: Retention Intron; SE: Skipped Exon. c Stacked bar graph of the proportion of different types of AKAP8-dependent alternative splicing events in epithelial and mesenchymal cells. d AKAP8-dependent SE events overlap with SEs altered during EMT (middle panel). Scatterplots of ∆PSI values between EMT-regulated SEs and AKAP8-dependent differential SEs identified in epithelial cells (left panel) and mesenchymal cells (right panel). SEs regulated during EMT and by AKAP8 in epithelial cells are highly negatively correlated (R = − 0.85, P = 1.93e-17), whereas those in mesenchymal cells are not correlated (R = 0.00, P = 0.98). P values were determined by hypergeometric test. e 96.6% (56/58) of epithelial AKAP8 differential SEs are discordant with EMT compared with 53.8% (28/52) of mesenchymal events. P < 0.0001 (P computed by Fisher’s exact test). f AKAP8 knockdown in epithelial cells causes upregulation of genes that are upregulated during EMT (left panel), and AKAP8 knockdown in the mesenchymal state results in downregulation of genes that are downregulated during EMT (right panel). Source data are provided as a Source Data file.