Effects of IWR-1 on the transcriptome of bovine embryonic stem cells and mouse embryonic fibroblasts

The use of tankyrase inhibitors is essential for capturing livestock embryonic stem cells (ESC), yet their mechanisms of action remain largely uncharacterized. Previous studies indicate that their roles extend beyond the suppression of canonical WNT signaling. This study investigates the effects of the tankyrase inhibitor IWR-1 on the transcriptome of bovine embryonic stem cells (bESC) and mouse embryonic fibroblasts (MEF). We performed RNA-seq analysis on day 1 treated bESC and the co-cultured MEF. Comparing the transcriptomes of cells cultured in complete medium (IWR) and IWR-1-removed medium (IWRR), we identified small fractions of exclusively expressed genes in both bESC and MEF. Regulators of HIPPO pathways TEAD4, AMOTL2, and AJUBA and HIPPO targeted gene CYR61 were differentially expressed in bESC. We also found that IWR-1 altered expression of 8 genes in MEF associated with signaling pathways activated by TGF-β ligands, including Gdf6, Inhbb, Bmp4, Fst, Inhba, Thbs1, Tgfb1, and Bmp2.