Analysis of Control and Liver-specific Mier1 KO Liver Transcriptomes after 70% Partial Hepatectomy

To explore how Mier1 affiects liver regeneration, we specifically knocked out Mier1 in mouse liver through adeno-associated virus (AAV). The mice we used were knocked in a Cre-induced Cas9 expression cassette. Through tail vein injection, we delivered the AAV expressing Cre-recombinase under TBG promoter, and sgRNA targeting Mier1 (AAV-Mier1 sgRNA), into the adult Cas9 knockin mice to knock out the Mier1 gene in liver. AAV vectors with no sgRNA inserted (AAV-Cre) were used in control animals. To assess the role of MIER1 in liver regeneration, we performed 70% partial hepatectomy, 3 weeks after AAV injection. We then performed RNA sequencing analysis on liver tissues collected from control and Mier1 ko groups at 0 h, 24 h, 36 h, 48 h and 72 h after partial hepatectomy. Interestingly, although MIER1 depletion did not cause a significant difference in expression of cell cycle genes before surgery, the increase of cell cycle gene expression during liver regeneration was significantly enhanced after MIER1 loss. Further analysis showed that after partial hepatectomy, MIER1 loss caused significant upregulation of genes enriched in cell proliferation relevant pathways. Overall design: Liver RNA profiles of WT and liver-specific Mier1 KO mice at different time points after partial hepatectomy were generated by deep sequencing. Each sample contained pooled RNA from three biological replicas that were mixed with an equal mass of RNA. Two samples from each group were included for sequencing.