Abstract

An AAV8-based bioluminescent reporter enables longitudinal monitoring of hepatic YAP/TAZ–TEAD activity in vivo . • Hepatic YAP/TAZ–TEAD activity exhibits biphasic dynamics during CCl₄-induced liver injury and fibrosis. • Hepatocyte-specific YAP deletion markedly attenuates TEAD-dependent transcriptional activity. YAP/TAZ are central mechanosensitive regulators of liver injury, fibrosis, and regeneration; however, their dynamic activity in vivo remains challenging to monitor. Here, we establish an AAV8-delivered bioluminescent reporter system (rAAV-8 × GTIIC-Luc) that enables real-time, non-invasive, and longitudinal visualization of hepatic YAP/TAZ-TEAD transcriptional activity. Small-molecule inhibitors targeting the upstream kinases LATS1/2 were employed to pharmacologically perturb YAP/TAZ activity, resulting in robust induction of reporter activity both in cultured cells and in mouse liver. Using a carbon tetrachloride (CCl₄)–induced mouse model of liver injury and fibrosis, we observed a characteristic biphasic pattern of hepatocellular YAP/TAZ–TEAD transcriptional activity, with an early increase followed by a gradual decline during continued injury and a further reduction upon CCl₄ withdrawal. Genetic ablation of YAP in hepatocytes markedly attenuated reporter signals throughout this process, supporting a dominant contribution of YAP to TEAD-dependent transcriptional programs in this context. Together, these results establish rAAV-8 × GTIIC-Luc as a robust platform for in vivo monitoring of YAP/TAZ–TEAD transcriptional dynamics and provide temporal insights into pathway regulation during liver injury, with broad applicability for mechanistic studies and drug evaluation.