RNA-seq on biliary epithelial cells (BECs) of Klf5 LKO mice upon DDC injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97167 | GEO | 2018/03/16
REPOSITORIES: GEO
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Project description:Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. In this study we posited that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanating from recruited macrophages restrains DR cell expansion by apoptosis, thereby limiting cholestatic liver injury. Cholestatic liver injury was induced in Wild type (WT), Trailfl/fl and in myeloid-specific Trail deleted (TrailΔmye) C57BL/6 mice using the DDC diet. The DDC diet induced injury and hepatomegaly. However, parameters of liver injury, fibrosis, ductular reaction and inflammation were all increased in the TrailΔmye mice as compared to the WT and Trailfl/fl mice. To better resolve the gene expression profile of cholangiocytes that may promote the recruitment of myeloid cells into the periportal neighborhood, we performed spatial transcriptomics on FPPE liver tissue sections from WT and TrailΔmye mice that were fed the control or DDC diet using the NanoString GeoMx DSP platform (Cat. No. 121401103, GeoMx NGS RNA WTA Mm).
2024-01-31 | GSE239667 | GEO
Project description:RNA-seq on biliary epithelial cells (BECs) of Klf5 LKO mice upon DDC injury
| PRJNA380876 | ENA
Project description:Background and aims: Liver is a major target organ for alcohol-induced disease and the spectrum of pathological states elicited by alcohol in liver comprises steatosis, alcoholic steatohepatitis, progressive fibrosis and cirrhosis, conditions that may progress to hepatocellular carcinoma. Many experimental animal models of alcoholic steatohepatitis exist that vary in duration, mode of alcohol administration and the degree and types of liver injury produced. While most of these models, regardless whether alcohol is administered through liquid diet or intragastrically, produce steatohepatitis and mild fibrosis, it is widely acknowledged that these models fail to fully recapitulate key characteristics of severe forms of alcoholic liver disease, such as alcoholic hepatitis. Recent studies attempted to combine alcohol and fibrosis and achieved promising results in mouse models that achieve some of the key features of alcoholic liver disease accompanied by exacerbated fibrosis and acute renal injury. This study combined a chronic cholestatic liver fibrosis model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) with a mouse model of intragastric alcohol feeding. Methods: Adult male C57BL6/J mice were treated with 3,5-diethoxycarbonyl-1,4-dihydrocolidine (DDC) containing diet (0.05% w/w) to induce chronic liver fibrosis. Following DDC-induced fibrogenesis, ethyl alcohol (EtOH) (up to 27 g/ kg/day, up to 28 days) was administered continuously to mice via a gastric feeding tube (Tsukamoto-Frenchmodel of alcoholic liver disease). Results: Exposure to DDC or EtOH alone resulted in liver fibrosis or steatosis, respectively. Combined treatment with DDC and EtOH lead to an additive effect on liver injury, as evident by the development of hepatic inflammation, steatosis, and pericellular fibrosis, and by increased serum transaminase levels, compared to mice treated with either agent alone. Liver transcriptomic changes specific to combined treatment group included pathways involved in the cell cycle and DNA damage. Analyses of feces from these mice revealed alcohol-associated changes to the bile acid profile and gut microbiome. Conclusions: Mice treated with DDC and EtOH displayed several key characteristics of human alcoholic hepatitis, including pericellular fibrosis, increased hepatic bacterial load with dysbiosis, reduced capacity of the microbiome to synthesize secondary bile acids.
2018-09-14 | GSE119953 | GEO
Project description:Increasing studies suggested the treatment potential of mesenchymal stem cells in variety diseases. Evidence showed that MSCs could promote injured tissue repair and improve disease mortality. These indicated that MSC transplantation may be an ideal candidate for cholestasis treatment.We found that MenSC transplantation could significantly improve the symptoms and pathological changes of DDC-induced cholestasis liver injury in mice.
2022-02-16 | PXD028425 | Pride
Project description:Following liver injury, a subset of hepatocytes adopt features of biliary epithelial cells (BECs) in a process known as biliary reprogramming. The aim of this study is to elucidate the molecular events accompanying this dramatic shift in cellular identity. Wild type hepatocytes, wild type biliary cells, DDC-treated hepatocytes, DDC-treated biliary cells, and DDC-treated reprogrammed cells were isolated by FACS, RNA isolated, and sequenced.
2020-08-27 | GSE156894 | GEO
Project description:Purpose: Cholestatic liver injury is associated with intrahepatic biliary fibrosis, which can progress to cirrhosis. Resident hepatic progenitor cells (HPCs) expressing Prominin-1 (Prom1/CD133) become activated and participate in the expansion of cholangiocytes known as the ductular reaction. Previously, we demonstrated that in biliary atresia, Prom1(+) HPCs are present within developing fibrosis and that null mutation of Prom1 significantly abrogates fibrogenesis. Here, we hypothesized that these activated Prom1-expressing HPCs promote fibrogenesis in cholestatic liver injury. Methods: Using Prom1CreERT2-nLacZ/+;Rosa26Lsl-GFP/+ mice, we traced the fate of Prom1-expressing HPCs in the growth of the neonatal and adult livers and in biliary fibrosis induced by bile duct ligation (BDL). Results: Prom1-expressing cell lineage labeling with Green Fluorescent Protein (GFP) on postnatal day 1 exhibited an expanded population as well as bipotent differentiation potential towards both hepatocytes and cholangiocytes at postnatal day 35. However, in the adult liver, they lost hepatocyte differentiation potential. Upon cholestatic liver injury, adult Prom1-expressing HPCs gave rise to both PROM1(+) and PROM1(-) cholangiocytes contributing to ductular reaction without hepatocyte or myofibroblast differentiation. RNA-sequencing analysis of GFP(+) Prom1-expressing HPC lineage revealed a persistent cholangiocyte phenotype and evidence of Transforming Growth Factor-b pathway activation. Conclusion: Our data indicate that Prom1-expressing HPCs promote biliary fibrosis by activation of myofibroblasts in cholestatic liver injury.
2020-06-30 | GSE144726 | GEO
Project description:Purpose: The goal of this study is to investigate the effect of recombinant human Cytoglobin (rhCYGB) on liver fibrosis induced by DDC diet in mice. Method: mRNA profiles of liver tissue of DDC-control mice and liver tissue of DDC-rhCYGB treated mice treated were generated by deep sequencing. Results: The RNA-seq data confirmed that extracellular matrix-encoding genes and fibrosis-related genes were down-regulated by the His-CYGB treatment.
2020-08-25 | GSE156778 | GEO
Project description:Analysis of gene expression in mouse E15.5 embryonic heart tissue, either wildtype, Ddc-/+ (maternal transmission of Ddc^Gt(OST129277)Lex knockout allele), Ddc+/- (paternal transmission), or Ddc-/-.
2016-10-05 | GSE87595 | GEO
Project description:Background and Aims: During severe or chronic hepatic injury, biliary epithelial cells (BECs), also known as cholangiocytes, undergo rapid reprogramming and proliferation, a process known as ductular reaction (DR), and allow liver regeneration by differentiating into both functional cholangiocytes and hepatocytes. While DR is a hallmark of chronic liver diseases, including advanced stages of non-alcoholic fatty liver disease (NAFLD), the early events underlying BEC activation are largely unknown. Since NAFLD initiates with increased lipid accumulation, a stage called steatosis; we hypothesized that BECs isolated directly from steatotic livers might address current knowledge gaps in early BEC activation. Approach and Results: Here, we used methods allowing isolation and extensive transcriptional characterization of BECs from chow diet (CD)- and high-fat diet (HFD)-fed mice livers. We demonstrate that BECs readily accumulate lipids during HFD feeding and that lipid overload induces the conversion of adult cholangiocytes into active BECs through upregulation of the cell cycle and DNA replication signature. This event is accompanied by significant downregulation of extracellular matrix organization in BECs derived from HFD-fed mice livers but not CD-fed mice livers. Mechanistically, we found that lipid overload unleashes the activation of the E2F transcription factors in BECs, which drives cell cycle progression.
2023-03-22 | GSE217739 | GEO
Project description:Transcriptomic analysis of Tregs from RelB-dDC mice
| PRJNA556427 | ENA