sc-RNA sequencing data of primary liver cells from wildtype, YAPKO,TAZKO and DKO mice
Background & Aims The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are promising targets for cancer therapy. However, it is not understood if inhibition of one factor is compensated by the activation of the other and if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver-resident cells. Methods Mice with hepatocyte (HC)-/biliary epithelial cell (BEC)-specific deletions of YAP and/or TAZ were generated (YAPKO, TAZKO and double knock-out (DKO)). Liver tissues were investigated by histology, immunohistochemistry, and single cell RNA-sequencing (scRNA-seq). Serum samples were analyzed using a cytokine array. Results Liver tissues from YAPKO and DKO mice were characterized by the loss of BECs, liver fibrosis, and necrosis. This phenotype was weakened in DKO tissues compared to specimen from YAPKO animals. YAP expression was induced in different non-parenchymal cells (NPCs) after YAP-depletion in HCs and BECs. Activation of YAP in Kupffer cells (KCs) and endothelial cells (ECs) in subclusters with specific molecular features was independent of cholestasis. Pro-inflammatory chemokines and cytokines such as interleukin-1 (IL1) and intercellular adhesion molecule-1 (ICAM1) were detected in the serum of YAPKO animals. YAP-interacting TEA domain transcription factor (TEAD) family members bound promoter regions of different secreted factors and may contribute to a severe inflammatory response in mice with YAP-inactivation in HCs and BECs. Conclusions YAP inactivation causes severe liver damage in vivo and concomitant TAZ deletion does not enhance but moderately reduce this phenotype. Furthermore, we describe a new mechanism how YAP inactivation in HCs/BECs contributes to YAP-driven heterologous cell communication originating from NPCs. Overall design: sc-RNA sequencing data were generared from primary liver cells of  wildtype (n=1), YAPKO(n=1),TAZKO(n=1) and DKO (n=1) mice