Fig. 3: TYK2 negatively regulates KRAS expression.
From: The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α
a Schematic for bulk RNAseq experiments for WT and TYK2 KO cells (n = 3). The figure was generated using Servier Medical Art. b Principal component (PC) analysis of the bulk RNA-seq samples. Filled circles, WT cells; empty circles, KO cells. p-value (linear regression comparison) PC1~genotype of Stage (S) 5 is indicated. c Volcano plot for S5 differentially expressed genes for WT and KO. Significantly downregulated genes, iris blue; upregulated genes, soft red. Selected genes of interest are highlighted. d, e FPKM values for NEUROG3 and NKX2-2 expression at different differentiation stages. p-value (DESeq2) is indicated for S5. f Selected up- and down- regulated Reactome enrichment pathways in S5 KO cells compared to WT. g FPKM values for KRAS expression. h Relative transcript levels of KRAS with qRT-PCR in hiPSCs, S4 and S5 cells. i Immunoblot for KRAS at S4 and S5. Normalization with tubulin densitometric values are indicated in the panel (n = 3). j Immunoblot for KRAS at S4 in WT and KO cells following TYK2i treatment during S3–S4. k Densitometric analysis of panel j (n = 3). l Correlation of TYK2 and NEUROG3 expression in human fetal pancreas (n = 16). Pearson’s correlation after log normalization of counts. m Correlation of KRAS and TYK2 expression; and n KRAS and INS expression in human islets (n = 191). Pearson’s correlations r and significance levels p are indicated in the panels. o Schematic of TYK2 overexpression experiments. p Immunoblot for TYK2 48 h post pCMV-TYK2 electroporation during S5. β-actin used as a loading control (n = 2). qRT-PCR relative transcript levels 24 h post pCMV-TYK2 overexpression during S5 for q TYK2, r KRAS, and s NEUROG3 (n = 3). Two-tailed unpaired t-tests were applied. *p < 0.05; **p < 0.01; ***p < 0.001; ns—non-significant. The boxplots in d, e, g, h and k showing the median with lower and upper hinges corresponding to the first and third quartiles (the 25th and 75th percentiles) with min to max whiskers (n = 3), except for h, (n = 4). Source data are provided as a Source Data file.
