Project description:We compared RNA expression profiles of wild type of mice maintained on high fat diet or Irs1/2:foxo1-LTKO mice infected with Fst288 AAV-TBG virus Fst288-AAV-TBG infection modestly up- or down-regulated the expression of many genes, including several related to hepatic glucose metabolism (Pck1, G6pc and Gck) (Fig. S8a); qPCR confirmed that Fst288AAV•TBG affected the expression of these and other genes during both fasting (Pck1, G6pc and Gck) and feeding (Foxo1, Igfbp1, Pck1, and Ppargc1a)
Project description:To explore the effect of Bicd2 in Con A-induced acute autoimmune hepatitis, we conducted single cell RNA sequencing of AAV-scramble or AAV-shBicd2 infected mice livers in response to Con A injection.
Project description:To explore how Mier1 affects 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 ATAC-seq in Control and Mier1 liver-sepcific knockout mice liver tissues at 0 h and 24 h after PHx to explore the influence of Mier1 on the chromation opening during liver regeneration.
Project description:Analysis of changes in gene expression following hepatocyte specific deletion of GATA4 in adult mice. Results showed that the subset of differentially expressed genes had liver specific ontologies. Total RNA isolated from hepatocytes of AAV8-Tbg-Cre injected GATA4 fl/fl mice was compared to total RNA isolated from AAV-Tbg-GFP injected GATA4 fl/fl mice.
Project description:Analysis of changes in gene expression following hepatocyte specific deletion of GATA4 and GATA6 in adult mice. Results showed that the subset of differentially expressed genes had liver specific ontologies. Total RNA isolated from hepatocytes of AAV8-Tbg-Cre injected GATA4,6 fl/fl mice was compared to total RNA isolated from AAV-Tbg-GFP injected GATA4,6 fl/fl mice.
Project description:This study reports the baseline effects of systemic (i.v.) administration of AAV8-TBG-null and AAV8-TBG-Cre on the liver of male, wild-type C57Black6/J mice. We performed polyA RNAseq of whole liver lysates from mice 2, 4 and 7 days post AAV8-TBG-null or AAV8-TBG-Cre administration and compared their transcriptome with that of male mice of similar age that didn't receive any AAV8 (day 0). We report some changes in gene expression of genes related to circadian rythm and response to infection at certain timepoints. Our results demonstrate that AAV8-TBG vectors can have minimal effects on the murine liver transcriptome, something that needs to be considered and controlled when using this system for mouse experiments. Finally, we hope that this dataset will help other researchers to correctly interpret data obtained from mouse experimentation using AAV8-TBG vectors.
Project description:Diacylglycerol acyltransferase (DGAT)-2 catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs and DGAT2 overexpression might have the opposite effect. Mouse DGAT2 was overexpressed in C57Bl/6J mice using adeno-associated virus 8 (AAV8 and AAV-DJ). The tissue specificity of AAV8 and AAV-DJ was first evaluated. To confirm that AAV8 and AAV-DJ only infected hepatocytes and not other cells in liver, we carried out single cell sequencing of liver cells isolated from mice infected with AAV8-mCherry and AAV-DJ-GFP. The mCherry and GFP signals were highly expressed in hepatocytes and not in stellate, endothelial, or Kupffer cells.
Project description: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.
Project description:To explore how Mier1 influence the genome H3K27ac levels during liver regeneration, we performed H3K27ac chromatin immunoprecipitation followed by sequencing in control and liver-specific Mier1 ko liver tissues at 0 h and 24 h after 70% partial hepatectomy (PHx). 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.Then we performed 70% partial hepatectomy, 3 weeks after AAV injection. Consistent with the increased expression of cell cycle genes during liver regeneration, we observed increased signals of H3K27ac at 24 h after hepatectomy, especially near some cell cycle genes, after MIER1 depletion in liver tissue.
Project description:Liver firbrosis model of hepatocyte-specific FOXA2 knockout mice. Adeno-associated virus AAV8-TBG-Control or AAV8-TBG-Cre was injected via the tail vein of FOXA2flox/flox (FOXA2f/f) mice 2 weeks prior to CCl4 administration. Hepatic fibrosis was induced by injection of CCl4 twice per week for 4 weeks.