Gene expression profile at single cell level of liver immune cells from the liver Rcrin conditional knockout mice (Rcrin knockout) and Rcrin flox mice (WT)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE212742 | GEO | 2022/09/08
REPOSITORIES: GEO
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Project description:Gene expression profile at single cell level of liver immune cells from the liver Rcrin conditional knockout mice (Rcrin knockout) and Rcrin flox mice (WT)
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2023-10-03 | GSE230131 | GEO
Project description:Hepatocellular carcinoma (HCC), which accounts for 90% of all primary livers tumors, is the fourth most common cancer in the world. The development of HCC is a long-term and complex process, and uncovering the molecular mechanisms associated with HCC development is critical for the disease diagnosis, prevention, and treatment. Exploring these mechanisms using human HCC samples is desirable, but frequently impractical, with a number of limitations and shortcomings. The STAMTM (Stelic Institute & Co, Tokyo, Japan) mouse model of NASH-associated liver carcinogenesis is considered a useful and relevant model for investigating the molecular pathogenesis of NASH-derived HCC. This model resembles the human HCC development associated with progression from simple steatosis to NASH, fibrosis, and HCC. In the present study, by using high-throughput whole genome microarrays (SurePrint G3 Mouse Gene Expression v2, 8x60K; Agilent Technologies, Santa Clara, CA), we examined the transcriptomic profiles in the livers of STAMTM mice at different stages of liver carcinogenesis, including steatosis (6 week time interval), NASH (8 weeks), fibrotic stage (12 weeks), and in full-fledged HCC (20 weeks). The results of microarray analyses showed significant progressive changes in hepatic gene expression during the development of HCC. A total of 970, 1462, 2742, and 2857 of differentially expressed genes were identified in the livers at 6, 8, 12, and 20 weeks, respectively. Detailed analysis of these differentially expressed genes will benefit the understanding of the underlying mechanisms of non-alcoholic fatty liver disease-derived HCC. Transcriptomic profile in the liver of STAM mice at 6 weeks (steatosis; n=3), 8 weeks (steatohepatitis; n=3) 12 weeks (fibrosis; n=4) and 20 weeks (HCC-stage tumor tissue, n=4) weeks. Age-matched control samples were also analyzed.
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Project description:Regulation of alternative splicing (AS) is crucial for gene expression and enables a single transcript to yield multiple isoforms that increase transcriptome and proteome diversity. Dysregulated AS has been linked to the development of non-alcoholic fatty liver diseases (NAFLD). However, the splicing factors involved in hepatic homeostasis and their functional mechanisms remain to be further characterized. Here, we report that spliceosome component Usp39 plays a critical role in the regulation of hepatocyte lipid homeostasis. We found that Usp39 expression is downregulated in hepatic tissues of NAFLD and non-alcoholic steatohepatitis (NASH) subjects. We observed increased lipid accumulation, spontaneous steatosis and impaired autophagy, lipophagy in particular, in mice with hepatocyte-specific Usp39 deletion. Combined analysis of RIP-seq and RNA-seq data revealed that Usp39 regulates AS of several autophagy-related genes including Hsf1. More specifically, deletion of Usp39 resulted in alternative 5’ splice site selection of exon 6 in Hsf1 and consequently reduced expression. Hsf1 was also found to be downregulated in NAFLD/NASH mice and patients. Importantly, overexpression of Hsf1 restored lipophagy, attenuated lipid accumulation and alleviated NASH caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is crucial for sustaining lipophagy and lipid homeostasis in the liver.
2023-09-24 | GSE213633 | GEO
Project description:To investigate the role of hepatic Pck1 in diet-induced nonalcoholic steatohepatitis (NASH), liver-specific Pck1-knockout mice were developed with Alb-Cre. Wild-type (WT) and Pck1-cKO mice were fed a Chow diet (Research Diets, D12450J: 10% Kcal fat, with tap water) or NASH-inducing diet (Research Diets, D12492: 60% Kcal fat, with drinking water containig 23.1 g/L fructose and 18.9 g/L glucose) for 24 weeks. RNA was extracted from the livers of mice from all treatment groups and used for RNA seqencing. RNA-seq data demonstrated that gluconeogenic enzyme PCK1 deficiency played an important role in the development of NASH.
2023-02-07 | GSE162211 | GEO
Project description:Purpose: The goal of this study is to determine whether hepatic deletion of Mettl3 affects chromatin accessibility. Methods: Liver samples were pooled from livers of Mettl3 HKO and Mettl3 flox/flox mice (n=4 for each group). Nuclei was extracted from liver samples, and the nuclei pellet was resuspended in the Tn5 transposase reaction mix. The transposition reaction was incubated at 37°C for 30 min. Equimolar Adapter1 and Adatper 2 were added after transposition, PCR was then performed to amplify the library. After the PCR reaction, libraries were purified with the AMPure beads and library quality was assessed with Qubit. The clustering of the index-coded samples was performed on a cBot Cluster Generation System using TruSeq PE Cluster Kit v3-cBot-HS (Illumina) according to the manufactuer’s instructions. After cluster generation, the library preparations were sequenced on an Illumina NovaSeq 6000 platform and 150 bp paired-end reads were generated. ATAC-seq analysis was performed using a standard protocol. Results: The hepatic chromatin accessibility in Mettl3 flox/flox and HKO mice were characterized.
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Project description:Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions, which underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDC), and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NALFD/NASH spectrum showed that cDC type 1 (cDC1) were more abundant and activated in disease. Genomic analysis of cDC-T pairs in liver draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1 blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH, and identifies XCR1+ cDC1 as an important driver of liver pathology.
2021-05-21 | GSE169445 | GEO