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. 2022 May 19;13:2791. doi: 10.1038/s41467-022-30489-z

Fig. 1. RNA splicing is dysregulated following Wnt hyperactivation.

Fig. 1

a RNAseq performed on wild-type and Apcfl/fl mouse small intestines isolated 5 days post tamoxifen inductions and sequences were subjected to biological pathway enrichment analysis. b Alternative splicing events following Apc-deletion compared to wild-type. c RT-PCR validation of a selection of alternative splicing events. d Representative images of wild-type and Apcfl/fl intestinal organoids treated with the splicing inhibitor pladienolide B. Scale bar 250 µm. e Half maximal inhibitory concentration (IC50) of pladienolide B in intestinal organoids, n = 3 independent experiments. f Representative images of organoids derived from normal human colon and 2 colonic tumours treated with 1 nM pladienolide B. Scale bar 1000 µm. g Quantification of viability assays following pladienolide B treatment, n = 3 independent experiments. h Schematic explanation of CRISPR screen design. i Guide RNA enrichment or depletion in surviving Apcfl/fl organoids compared to wild-type following completion of CRISPR screen. Data represented as mean and error bars SD. Data analysed with two-tailed, unpaired t-test, p values are indicated in figure panels. See also Fig. S1.