Effect of knockdown Tbl1xr1 on gene expression after 2/3 hepatectomy
Our spatiotemporal data confirmed activation of Tbl1xr1 in hepatocytes after 2/3 hepatectomy. TBL1XR1 is a transcriptional cofactor inducing ubiquitination and degradation of NCoR/SMRT co-repressors and NCoR is a negative regulator of hepatocyte proliferation acting through histone deacetylases (HDACs). We have examined the role of TBL1XR1 in liver regeneration through in vivo shRNA knockdown using adeno-associated viruses (shNC and shTbl1xr1) specifically targeting hepatocytes. The knockdown of Tbl1xr1 results in impair hepatocyte proliferation.To investigate the downstream targets of TBL1XR1 during liver regenration, we here perform the bulk RNA-seq for shNC and shTbl1xr1 at D2 after hepatectomy. Our data show demonstrated that Tbl1xr1 knockdown not only led to reduced cell cycle genes but also to impaired fatty acid ß-oxidation as the most obviously affected liver function. Overall design: To examine the role of TBL1XR1 in liver regeneration, we performed in vivo shRNA knockdown (shNC and shTbl1xr1) using adeno-associated viruses specifically targeting hepatocytes. Four weeks post-infection we performed PHx and extracted the liver at D2 for bulk RNA-seq.