Hepatic transcriptome of RuvBL1hep+/- mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB34908 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3687445_1.fastq.gz | Fastqsanger.gz | |||
| ERR3687445_2.fastq.gz | Fastqsanger.gz | |||
| ERR3687446_1.fastq.gz | Fastqsanger.gz | |||
| ERR3687446_2.fastq.gz | Fastqsanger.gz | |||
| ERR3687447_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Many plant-derived bioactive molecules with low solubility and permeability can cause hepatocyte injury. However, the mechanism by which they induce hepatic damage without passive diffusion into the hepatic circulatory system remains unclear. In this study, we demonstrate that indirubin, the main component of indigo naturalis with poor aqueous solubility, predisposes mice with chronic colitis to hepatic injury. This closely mimics the hepatic damage commonly observed in ulcerative colitis patients treated with indigo naturalis. To elucidate the mechanism of indirubin-induced hepatocyte injury in chronic colitis, we performed bulk RNA sequencing on hepatic tissues from DSS-induced colitis mice treated with a sublethal indirubin dose.
2025-06-15 | GSE299769 | GEO
Project description:The liver is the central organ critically regulating the balance of the metabolically potent yet toxic bile acids in the body. While genomic association studies have pointed to hepatic Sel1L – a critical component of mammalian Hrd1 ER-associated degradation (ERAD) machinery – as an influencer of serum bile acid levels, physiological relevance and mechanistic insights of ERAD in bile homeostasis remain unexplored. Using hepatocyte-specific Sel1L-deficient mouse models, we report that hepatic Sel1L-Hrd1 ERAD critically manages bile homeostasis in the body. Mice with hepatocyte-specific Sel1L developed intrahepatic cholestasis, with significant overload of bile acids in the liver and circulation under basal condition, and were hypersensitive to dietary bile acid challenge. By contrast, biliary bile acid and phosphatidylcholine levels were reduced, pointing to an export defect from hepatocytes. Unbiased proteomics analysis followed by biochemical assays revealed significant accumulation of the bile-stabilizing phosphatidylcholine exporter ATP-binding cassette 4 (Abcb4) in the ER of Sel1L-deficient livers, a gene associated with Progressive Familial Intrahepatic Cholestasis type III. Indeed, Abcb4 was a substrate of Sel1L-Hrd1 ERAD. Hence, hepatic Sel1L-Hrd1 ERAD maintains bile equilibrium via quality control of Abcb4 maturation in the ER.
2023-03-11 | PXD035243 | Pride
Project description:Previously we observed that when constantly reducing protein synthesis using the whole-body eIF2α haploinsufficient mouse model, the hepatic lipogenesis process would gear down. To figure out whether translation can regulate lipogenesis in a cell-autonomous way, we created the liver-specific eIF4EBP3 deficient mouse by adenovirus-mediated shRNA targeting Eif4ebp3. eIF4EBP3 suppresses translation initiation by sequestering eIF4E. Therefore, by knocking down it, we established a translation hyperactive state in liver.
2022-03-01 | GSE146153 | GEO
Project description:Notch signaling regulates cell-fate decisions in several developmental processes and cell functions. However, a role for Notch in hepatic thrombopoietin (TPO) production remains unclear. We noted thrombocytopenia in mice with hepatic Notch1 deficiency, and so investigated TPO production and other features of platelets in these mice. We found that the liver ultrastructure and hepatocyte function were comparable between control mice and Notch1-deficient mice. However, the Notch1-deficient mice had significantly lower plasma TPO and hepatic TPO mRNA levels, concomitant with lower numbers of platelets and impaired megakaryocyte differentiation and maturation, which were rescued by addition of exogenous TPO. Additionally, JAK2/STAT3 phosphorylation was significantly inhibited in Notch1-deficient hepatocytes, consistent with the RNA-seq analysis. JAK2/STAT3 phosphorylation and TPO production was also impaired in cultured Notch1-deficient hepatocytes after treatment with desialylated platelets. Consistently, hepatocyte-specific Notch1 deletion inhibited JAK2/STAT3 phosphorylation and hepatic TPO production induced by administration of desialylated platelets in vivo. Interestingly, Notch1 deficiency downregulated the expression of HES5 but not HES1. Moreover, desialylated platelets promoted the binding of HES5 to JAK2/STAT3, leading to JAK2/STAT3 phosphorylation and pathway activation in hepatocytes. Hepatocyte Ashwell-Morell receptor (AMR) (asialoglycoprotein receptor 1, ASGR1) physically associates with Notch1 and inhibition of AMR impaired Notch1 signaling activation and hepatic TPO production. Furthermore, blockage of Dll4 on desialylated platelets inhibited hepatocyte Notch1 activation and HES5 expression, JAK2/STAT3 phosphorylation and subsequent TPO production. In conclusion, our study identifies a novel regulatory role of Notch1 in hepatic TPO production, indicating that it might be a target for modulating TPO level.
2024-04-12 | GSE250529 | GEO
Project description:Hepatic transcriptome analysis of control and severe acute pancreatitis mice
| PRJNA759329 | ENA
Project description:The liver is essential for fatty acid utilization during fasting. Fatty acids released by lipolysis from adipose tissue during fasting are taken up from the blood by hepatocytes and esterified as triacylglycerols for oxidative metabolization and ketogenesis. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, transport of non-esterified fatty acids (NEFAs) from the liver sinusoidal lumen to the hepatocyte is not. Here, we show that murine hepatic stellate cells (HSCs), enveloping the liver sinusoids as pericytes, and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic NEFA uptake during fasting. HSC-specific ablation of PLVAP suppresses hepatocyte fatty acid esterification to di- and triacylglycerols along with fasting fatty acid utilization and ketogenesis. Consistently, single cell-resolved transcriptomics further revealed severe perturbation of hepatocyte gene programs governing normal fatty acid handling, oxidation, and ketogenesis. By super-resolution microscopy we localized HSC PLVAP to caveolae residing along the sinusoidal lumen strongly supporting a role for PLVAP in caveolar transcytosis of NEFAs across HSCs and hence the sinusoid wall as rate-limiting for hepatic fatty acid utilization during fasting. This was supported by a similar decline in neutral lipid droplet formation in livers of fasting Caveolin-1 knockout mice. Altogether, our study shows vital roles for PLVAP and for HSCs in normal fasting metabolism of liver.
2025-03-07 | PXD046745 | Pride
Project description:In addition to immunodeficiency, host mice for chimeric mice with highly humanized liver should have hepatic malfunction in order to allow higher replacement rate of human hepatocytes in the liver. Urokinase-type plasminogen activator (uPA) whole gene transfer is often employed to achieve hepatic malfunction in the host mice. We have established uPA cDNA transfer that is far stable, as compared with traditional whole uPA gene transfer. Hepatic gene expression was quite similar between whole uPA gene transfer and uPA cDNA transfer after transplantation of the same lot of human hepatocyte (BD195),, as compared with the variation of gene expression after transplantation of different lots of human hepatocytes to host mice with whole uPA gene transfer.
2015-06-17 | GSE69936 | GEO
Project description:Hepatic transcriptome of junctional adhesion molecule A knockout, F11r–/– mice fed a Western diet (WD) for eight weeks. A cohort of WD-fed mice were treated with IgG or α4β7 mAb for four weeks starting at week four following initiation of the WD.
2022-04-21 | GSE149208 | GEO
Project description:The liver has an exceptional capacity for regeneration which is crucial for maintaining liver function. Since transcriptional regulation of genes controlling metabolism and cell division is a hallmark of liver regeneration (LR), we investigated the role of Zinc-finger and homeboxes 2 (ZHX2), a transcription factor critical for regulating liver postnatal gene expression and hepatic lipid hemostasis, in LR. Our results show that hepatocyte-specific Zhx2 knockout (Zhx2-KOhep) enhances LR after 2/3 partial hepatectomy in mice. Proteomics assays revealed higher mitochondrial oxidative phosphorylation (OXPHOS) in Zhx2-KOhep mouse livers. Oxygen consumption rate (OCR) and ATP generation assays confirmed the enhanced OXPHOS in Zhx2-KOhep mouse livers and human hepatocytes with ZHX2 knockdown.
2023-10-17 | PXD027897 | Pride
Project description:Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in LDLR-/- mice. In addition, compared to controls, livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting reduced mitochondrial oxidative capacity. Proteome dynamics analysis revealed that mitochondrial dysfunction is associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41±0.46 vs. 5.15±0.49 day, P<0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome c oxidase subunit 4 isoform 1 of complex III (5.9 ± 0.1 vs 3.4 ± 0.8 day), ATP synthase subunit α (6.3±0.4 vs. 5.5±0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5±0.6 vs. 6.5±0.2 day) (P<0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities, suggesting that increased degradation of mitochondrial proteins contributed to hepatic mitochondrial dysfunction in NAFLD mice. Autophagy, but not proteasomal degradation, contributed to increased clearance of hepatic mitochondrial proteins in NAFLD mice. In conclusion, the proteome dynamics approach suggests that alterations in mitochondrial proteome dynamics is involved in hepatic mitochondrial dysfunction in NAFLD.
2018-11-21 | PXD008766 | Pride