Transcriptomic profiling of liver tissues from DDC-treated and control mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE337823 | GEO | 2026/07/13
REPOSITORIES: GEO
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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: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:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at four time points: baseline, at day 14 of DDC treatment, and following a 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230091 | GEO
Project description:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at six time points: baseline, at days 7 or 14 of DDC treatment, and following a 7-, 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230085 | GEO
Project description:The liver biliary niche serves as a reservoir of tissue-resident immune cells and supports tissue fibrosis upon damage, yet the role of peribiliary immune cells during cholangitis remains poorly understood. Here, we induce cholestatic liver injury mirroring human biliary diseases with bile acid retention in mice to establish a spatial and multimodal single-cell RNA sequencing atlas of the liver and liver-draining lymph nodes (LN). We characterized a hepatic disease state trajectory from dendritic cell precursors (preDCs) to a mature subset of pro-inflammatory Mgl2+ type 2 conventional dendritic cells (cDC2B) and observed dynamic crosstalk with γδ T cells inducing an Il17 response (γδ T17). Dissection of the cDC2B-γδ T cell communication node identified the Icosl-Icos pair as an important cell contact-dependent interaction, which was validated in vitro. In vivo, cDC2B depletion attenuated γδ T17 responses in cholestatic liver injury, and liver fibrosis was reduced in a model of inducible γδ T cell depletion and in an Il17-deficient background. Our work demonstrates dynamic turnover of cDC2 within the biliary niche during cholestasis, and a profibrogenic function of γδ T cells contingent on the induction by peribiliary cDC2B, highlighting relevant disease determinants within the immunobiliary and liver-draining LN niche. Spatial Transcriptomics Data (Xenium Platform) of Mouse Liver tissues treated with DDC diet for 5 days.
2026-02-17 | GSE311681 | GEO
Project description:In other to assess functional involvement of Klf5 in DR regulation, we made liver-specific Klf5 knockout mice. Ductular reaction upon cholestatic liver injury is severely suppressed in these mice. We conducted RNA-seq analysis on the BECs from control mice and Klf5 LKO mice upon DDC injury to further elucidate the Klf5 functions.
2018-03-16 | GSE97167 | GEO
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: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:Transcriptomic profiling of liver tissues from DDC-treated and control mice
| PRJNA1491187 | ENA
Project description:Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with increased risk of fibrosis and liver failure. The Receptor for Advanced Glycation End Products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing, mass spectrometry and in vitro analyses, we investigated the role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Employing mass spectrometry analyses of soluble factors of in vitro cultured wildtype and RAGE deficient BECs Notch ligand Jagged1 was found to be secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis.
2025-07-16 | PXD065854 | Pride