Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1023382 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26261505.fastq.gz | Fastqsanger.gz | |||
| SRR26261506.fastq.gz | Fastqsanger.gz | |||
| SRR26261507.fastq.gz | Fastqsanger.gz | |||
| SRR26261508.fastq.gz | Fastqsanger.gz | |||
| SRR26261509.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Nonalcoholic steatohepatitis (NASH) is a progressive liver disease that is characterized by liver injury, inflammation and fibrosis. NASH pathogenesis is linked to reprogramming of chromatin landscape in the liver that predisposes hepatocytes to stress-induced tissue injury. However, the molecular nature of the putative checkpoint that maintains chromatin architecture and preserves hepatocyte health remains elusive. Here we show that heterogeneous nuclear ribonucleoprotein U (hnRNPU), a nuclear matrix protein that governs chromatin architecture and gene transcription, is a critical factor that couples chromatin disruption to NASH pathogenesis. RNA-seq and ChIP-seq studies revealed an extensive overlap between hnRNPU occupancy and altered gene expression during NASH. Hepatocyte-specific inactivation of hnRNPU disrupted liver chromatin accessibility, activated the molecular signature of NASH and sensitized mice to diet-induced NASH pathogenesis. Mechanistically, hnRNPU deficiency stimulated the expression of a truncated isoform of TrkB that promotes inflammatory signaling in hepatocytes and stress-induced cell death. These findings illustrate a novel mechanism through which disruptions of chromatin architecture drive the emergence of disease-specific signaling patterns that promote liver injury and exacerbate NASH pathogenesis.
2019-09-10 | GSE131336 | GEO
Project description:We perform sc-RNAseq in NASH livers from WT and miR-33-AlbCRE conditional knock-out mice. Liver were isolated from mice after 6 months of feeding a choline deficient high fat diet to analyze the effect of miR-33 deficiency specifically in hepatocytes and the crosstalk between hepatocytes and other cell types in the liver.
2024-10-01 | GSE259277 | GEO
Project description:Current models of hepatocellular tumorigenesis propose that the chronic injury and inflammation in NASH are mutagenic and growth promoting which can eventually lead to HCC. However, contrary to this model, here we show that NASH suppresses the early development of liver cancers in mice. We found that NASH did not hinder the malignant reprogramming of oncogene expressing hepatocytes but suppressed their clonal expansion and led to their elimination. This elimination was not caused by a direct effect of NASH on malignant cells but due to the stimulation of cell competition in tumor-surrounding hepatocytes. Mechanistically, NASH activated the Hippo pathway effectors Yap and Taz in hepatocytes, which elevated their cellular fitness. Thus, deletion of Yap/Taz in tumor-surrounding hepatocytes abolished the elimination of tumor cells by NASH, while experimental hyperactivation of Yap in malignant cells protected them from NASH-induced elimination
2025-09-01 | GSE241856 | GEO
Project description:Current models of hepatocellular tumorigenesis propose that the chronic injury and inflammation in NASH are mutagenic and growth promoting which can eventually lead to HCC. However, contrary to this model, here we show that NASH suppresses the early development of liver cancers in mice. We found that NASH did not hinder the malignant reprogramming of oncogene expressing hepatocytes but suppressed their clonal expansion and led to their elimination. This elimination was not caused by a direct effect of NASH on malignant cells but due to the stimulation of cell competition in tumor-surrounding hepatocytes. Mechanistically, NASH activated the Hippo pathway effectors Yap and Taz in hepatocytes, which elevated their cellular fitness. Thus, deletion of Yap/Taz in tumor-surrounding hepatocytes abolished the elimination of tumor cells by NASH, while experimental hyperactivation of Yap in malignant cells protected them from NASH-induced elimination
2025-09-01 | GSE241855 | GEO
Project description:BACKGROUND & AIMS: Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. METHODS: Microarray was performed to identify differentially expressed genes in NASH. Quantitative real time PCR (qRT-PCR) was used to examine gene expression levels. Western blotting and immunofluorescence staining were employed to examine hemoglobin proteins. Flow cytometry was used to measure intracellular oxidative stress. RESULTS: Analysis of microarray gene expression data has revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopspies from NASH patients. Increased hemoglobin expression in NASH was validated by qRT-PCR. However, the expression of erythrocyte specific marker genes such as SPTA, SPTB, GYPA, GATA1, and ALAS2 did not change, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, induced a dose dependent increase in HBA1 expression in HepG2 cells. Intriguingly, forced hemoglobin expression suppressed oxidative stress. CONCLUSIONS: Oxidative stress upregulates hemoglobin expression in hepatocytes. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage. These findings suggest that hemoglobin is an inducible antioxidant in hepatocytes in response to increased oxidative stress as found in NASH livers. Twelve biopsy diagnosed NASH patients were included in this study. For control groups, total RNA from 5 different subjects were purchased from ADMET. These subjects are free from liver disease.
2010-10-20 | E-GEOD-24807 | biostudies-arrayexpress
Project description:Background and aims: NASH, characterized by inflammation and fibrosis, is emerging as a leading etiology of HCC. Lipidomics analyses in the liver have shown that the levels of polyunsaturated phosphatidylcholine (PC) are decreased in patients with NASH, but the roles of membrane PC composition in the pathogenesis of NASH have not been investigated. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a phospholipid (PL) remodeling enzyme that produces polyunsaturated PLs, is a major determinant of membrane PC content in the liver. Approach and results: The expression of LPCAT3 and the correlation between its expression and NASH severity were analyzed in human patient samples. We examined the effect of Lpcat3 deficiency on NASH progression using Lpcat3 liver-specific knockout (LKO) mice. RNA sequencing, lipidomics, and metabolomics were performed in liver samples. Primary hepatocytes and hepatic cell lines were used for in vitro analyses. We showed that LPCAT3 was dramatically suppressed in human NASH livers, and its expression was inversely correlated with NAFLD activity score and fibrosis stage. Loss of Lpcat3 in mouse liver promotes both spontaneous and diet-induced NASH/HCC. Mechanistically, Lpcat3 deficiency enhances reactive oxygen species production due to impaired mitochondrial homeostasis. Loss of Lpcat3 increases inner mitochondrial membrane PL saturation and elevates stress-induced autophagy, resulting in reduced mitochondrial content and increased fragmentation. Furthermore, overexpression of Lpcat3 in the liver ameliorates inflammation and fibrosis of NASH. Conclusions: These results demonstrate that membrane PL composition modulates the progression of NASH and that manipulating LPCAT3 expression could be an effective therapeutic for NASH.
2024-06-05 | GSE218075 | GEO