Yap1 mediates a systemic catabolic resonse during liver growth and repair
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE262617 | GEO | 2025/06/16
REPOSITORIES: GEO
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Project description:Yap1 mediates a systemic catabolic resonse during liver growth and repair
| PRJNA1092653 | ENA
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.
2022-12-31 | GSE212626 | GEO
Project description:Adeno-associated viral (AAV) small hairpin (shRNA) expression vectors are a promising therapeutic but can induce severe liver toxicity when delivered at high albeit undefined doses. Using various AAV-shRNA vectors under the high-expressing U6 and low-expressing H1 promoters, we found that dose-limiting toxicity was strongly correlated with an shRNA concentration of >12% of total microRNA levels. Toxicity was associated with a specific reduction in the first synthesized 22nt isoform of miR-122-5p, resulting in the specific de-repression of miR-122 target mRNAs. A causative link between miR-122 reduction and toxicity was established when an AAV-sh-miR-122 vector producing >20% of the total liver miRNAs prevented liver toxicity. Consistent with these results, miR-122 knockout mice, which in part adapt to an absence of miR-122 reduction, also show no toxicity with high dose AAV-shRNA delivery. RNA sequencing of 12 liver samples, 2 receiving H1-shRNAs, 7 with U6-shRNAs and 3 controls; small RNA sequencing of 95 samples including 18 with CMV-driven miR-122 expression in HEK293 cells, 13 in miR-122 knockout mice, 9 samples in mice heterozygous for miR-122, 5 samples with Cre-mediate excision of miR-122, 19 samples immunoprecipitated with Ago2 and 31 additional liver samples (3 control, 11 receiving H1-shRNAs and 17 receiving U6-shRNAs). Small RNA libraries were barcoded (first 4 nucleotides) at the 5' end and ligated to linker-1 (5'-CTGTAGGCACCATCAAT) at the 3' end.
2016-03-09 | E-GEOD-69186 | biostudies-arrayexpress
Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha-helix peptides that display similar functions to apolipoprotein A-I. Preclinical and clinical studies have demonstrated the safety and efficacy of apolipoprotein A-I mimetic peptides in multiple indications associated with inflammatory processes. In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.
2021-09-09 | PXD023281 | Pride
Project description:Adeno-associated viral (AAV) small hairpin (shRNA) expression vectors are a promising therapeutic but can induce severe liver toxicity when delivered at high albeit undefined doses. Using various AAV-shRNA vectors under the high-expressing U6 and low-expressing H1 promoters, we found that dose-limiting toxicity was strongly correlated with an shRNA concentration of >12% of total microRNA levels. Toxicity was associated with a specific reduction in the first synthesized 22nt isoform of miR-122-5p, resulting in the specific de-repression of miR-122 target mRNAs. A causative link between miR-122 reduction and toxicity was established when an AAV-sh-miR-122 vector producing >20% of the total liver miRNAs prevented liver toxicity. Consistent with these results, miR-122 knockout mice, which in part adapt to an absence of miR-122 reduction, also show no toxicity with high dose AAV-shRNA delivery.
2016-03-09 | GSE69186 | GEO
Project description:To explore how Mier1 affiects high-fat diet-fed, aging and adipose tissue Lipe knockout mice liver regeneration, we specifically knocked out liver Mier1 in high-fat diet-fed, aging and adipose tissue Lipe knockout mice 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 on high-fat diet-fed, aging and adipose tissue Lipe knockout mice. We then performed RNA sequencing analysis on liver tissues collected from control and Mier1 ko groups at 0 h, 48h or 36 h after partial hepatectomy. RNA-seq analysis showed that after partial hepatectomy, MIER1 loss caused significant upregulation of genes enriched in cell proliferation relevant pathways.
2022-12-31 | GSE212628 | GEO
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers. 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.
2013-11-25 | E-GEOD-49386 | biostudies-arrayexpress
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.
2022-12-30 | GSE188421 | GEO
Project description:Assay of gene expression pattern differences between liver cancer tissue and normal liver tissue from the same mouse by microarray in 4 separate mice injected with recombinant adeno-associated viral (AAV) vector 4 Mice (M24, M48, M50, M60) were necropsied at 18 months post-injection of AAV-vector, and livers removed. Tumor tissue and adjacent normal tissue were identified and dissected for RNA extraction.
2010-11-14 | E-GEOD-23680 | biostudies-arrayexpress
Project description:Hippo signaling pathway is pivotally involved in human cancer. Among the Hippo components, YAP1 is highly active while function of MST1,2 and SAV1 was lost in liver cancer. Based on systematic analysis, we identified KLF5 as YAP1 binding partner in silico. To investigate KLF5 in liver cancer, we performed the gene expression microarray after knocked down YAP1, TEAD1 and KLF5 in SK-Hep1 cell line. To identify the role of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line, we performed microarray after knocking down YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (3 siLuc, 3 siYAP1, 3 siTEAD1, 3 siKLF5)
2013-12-31 | E-GEOD-32597 | biostudies-arrayexpress