Peter van Mourik

35 R117H function and VX-770 response in organoids 0.0 0.2 0.4 0.6 0.5 1.0 1.5 2.0 2.5 Normalized R117H-CFTR mRNAexpression Normalized CFTR protein expression r=0.88 p<0.0001 0.5 1.0 500 1000 Normalized mRNAexpression Organoid swelling (AUC at 0.05 µ M Forskolin) r=0.57 p=0.04 1 2 3 4 0 500 1000 Normalized protein expression Organoid swelling (AUC at 0.05 µ M forskolin) r=0.56 p=0.04 0 1 2 3 4 0 500 1000 1500 2000 2500 Normalized protein expression Organoid swelling with VX-770 (AUC at 0.05 µ M forskolin) r=0.72 p<0.01 0.0 0.5 1.0 1.5 1000 2000 3000 4000 Normalized mRNAexpression Organoid swelling with VX-770 (AUC at 0.128 µ M forskolin) r=0.57 p=0.03 0 1 2 3 4 0 1000 2000 3000 4000 Normalized protein expression Organoid swelling with VX-770 (AUC at 0.128 µ M forskolin) r=0.60 p=0.02 0 1 2 3 4 0 500 1000 1500 2000 Normalized CFTR protein expression Vehicle-corrected organoid swelling with VX-770 (AUC at 0.05 µ M forskolin) r=0.69 p<0.01 0.0 0.5 1.0 500 1000 1500 2000 2500 Normalized mRNAexpression Vehicle corrected organoid swelling with VX-770 (AUC at 0. 28 µ M forskolin) r=-0.07 p=0.80 0 1 2 3 0 500 1000 1500 2000 2500 Normalized CFTR protein expression Vehicle corrected organoid swelling with VX-770 (AUC at 0.128 µ M forskolin) r=-0.05 p=0.89 20 40 60 80 0.0 0.5 1.0 1.5 Sweat chloride concentration (mmol/L) Normalized mRNA expression r=-0.44 p=0.16 0 20 40 60 80 0 500 1000 1500 2000 Sweat chloride concentration (mmol/L) Organoid swelling (AUC at 0.128 µ M Forskolin) r = -0.4 p = 0.17 20 40 60 80 0 500 1000 Sweat chloride concentration (mmol/L) Organoid swelling (AUC at 0.05 µ M Forskolin) r=-0.2 p=0.54 0 20 40 60 80 0 1 2 3 4 Sweat chloride concentration (mmol/L) CFTR Protein expression r = -0.60 p=0.03 A B C F E D G H I L K J M p.Arg117His / p.Arg117His p.Phe508del / p.Arg117His p.Arg1162X /p.Arg117His c.1857delT / p.Arg117His p.Arg553X / p.Arg117His p.Trp1282X / p.Arg117His Supplementary Figure 1 Supplementary figure 1. Correlation analyses between FIS, mRNA, and protein expression in R117H-CFTR organoids and sweat chloride concentration. Correlation analyses was performed for (A) normalized R117H-CFTR mRNA expression and normalized CFTR protein expression in compound heterozygous R117H organoids (B) normalized R117H-CFTR mRNA expression and organoid swelling after stimulation with 0.05 µM forskolin, (C) normalized CFTR protein expression and organoid swelling after stimulation with 0.05 µM forskolin, (D) normalized CFTR protein expression and organoid swelling in the presence of 3 µM VX-770 and 0.05 µM forskolin stimulation, (E) normalized R117H-CFTR mRNA expression and organoid swelling in the presence of 3 µM VX-770 and 0.128 µM forskolin, (F) normalized 2