In vitro expansion of cirrhosis derived liver epithelial cells reveals progenitor-like properties [methylation]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158612 | GEO | 2020/09/28
REPOSITORIES: GEO
Similar Datasets
Project description:Our goal is to in vitro expand mouse hepatocytes and human cirrhotic liver hepatocytes. Under the extreme culture condition, mouse hepatocytes proliferated and de-diffrentiated into progenitor cell like cells, moreover, the progenitor like cells could re-differentiate into hepatocytes in vivo. On the other hand, huamn cirrhotic liver cells could also expand and retain the probability of differentiate in vivo.
2021-08-28 | GSE182877 | GEO
Project description:Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine and colon. Here we derived organoids from mouse gallbladder tissue (gallbladder organoids), from mouse liver (including the extrahepatic biliary ducts and gallbladder; liver organoids) and from mouse small intestine tissue (intestinal organoids). RNA was prepared from these organoids and used to assay expression of 21,258 genes using Affymetrix gene expression arrays. RNA was also prepared from mouse gallbladder, liver and small intestine tissues and used to assay gene expression in these tissues. Finally, gallbladder organoids were induced to differentiate by removing R-spondin 1 and noggin from the culture media and subjected to gene expression array analysis. RNA was extracted from mouse gallbladder organoids, differentiated gallbladder organoids, liver organoids, small intestine organoids, gallbladder tissue, liver tissue and small intestine tissue and then used for hybridization of Affymetrix gene expression microarrays.
2016-04-06 | E-GEOD-77461 | biostudies-arrayexpress
Project description:Gene profiling of hepatocytes in early and advanced cirrhotic Rats Two-condition experiment, Advanced cirrhosis vs Control liver, Advanced cirrhosis vs Early cirrhosis. Biological replicates: 5 Advanced cirrhosis, 5 Early cirrhosis, 5 control liver. Each hepatocyte was isolated independently. One replicate per array.
2011-11-02 | E-GEOD-22977 | biostudies-arrayexpress
Project description:Gene profiling of hepatocytes in early and advanced cirrhotic Rats
2011-11-02 | GSE22977 | GEO
Project description:Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine and colon. Here we derived organoids from mouse gallbladder tissue (gallbladder organoids), from mouse liver (including the extrahepatic biliary ducts and gallbladder; liver organoids) and from mouse small intestine tissue (intestinal organoids). RNA was prepared from these organoids and used to assay expression of 21,258 genes using Affymetrix gene expression arrays. RNA was also prepared from mouse gallbladder, liver and small intestine tissues and used to assay gene expression in these tissues. Finally, gallbladder organoids were induced to differentiate by removing R-spondin 1 and noggin from the culture media and subjected to gene expression array analysis.
2016-04-06 | GSE77461 | GEO
Project description:Background & Aims: Since liver hepatocytes produce the majority of serum proteins, liver cirrhosis displays a massive alteration in serum proteome. The aim of the current study was to characterize these alterations and to study the prognostic usefulness of hepatocellular proteins available in routine clinical testing. Methods: Sera from 29 healthy controls and 43 cirrhotic subjects were subjected to untargeted proteomic analysis. The data were analyzed by Perseus program, R and unsupervised hierarchical clustering. The prognostic usefulness potential of selected biomarkers was tested in 61 controls and 285 cirrhotic individuals. Ingenuity pathway analysis (IPA) was employed to determine the upstream regulators that were further validated in 9 control and 9 cirrhotic livers. Results: Proteomics uncovered 65 down- and 16 upregulated hepatocellular serum proteins that are significantly down- respectively upregulated in cirrhotic subjects versus controls. Hierarchical clustering revealed two main clusters and 6 subclusters, while IPA identified HNF4α and IL6 as the two major upstream regulators that were confirmed in gene expression analyses. Pseudocholinesterase (AUROC 0.618; P=0.002), transferrin (AUROC 0.594; P=0.013), and transthyretin (TTR; AUROC 0.586; P=0.023) but not albumin serum levels discriminated between 90 days transplant-free survivors vs. non-survivors. Tree learning decision algorithm identified transthyretin as a biomarker that improved the prediction of death or transplant in the subset of patients with acute-on-chronic liver failure (ACLF). TTR≤58 mg/dl conferred an increased risk in both univariate (HR 1.75; 95% CI 1.14-2.67; P=0.01) and multivariable analysis (aHR 1.59; 95% CI 1.04-2.24; P=0.033). Conclusion: Our study uncovers the changes in hepatocellular serum proteins as well as the underlying transcriptional factors and suggest that transthyretin may constitute an useful prognostic adjunct in ACLF subjects.
2023-11-20 | PXD035024 | Pride
Project description:In variceal bleeding liver function deterioration is a major cause of death. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL) and CBDL rats pre-treated with 3 doses (5 mg*Kg-1*day-1) of simvastatin. Rats were submitted to H/R or sham procedure. Subsequently, livers were isolated and perfused for functional assessment of liver microcirculation. Liver transcriptome was assessed with microarrays. H/R significantly impaired endothelial-dependent vasorelaxation in cirrhotic (p=0.035) but not control livers. H/R induced a similar increase in ALT in control and cirrhotic rats, whereas the increase in AST was 10 times higher in cirrhotic than in control rats (p=0.007). Simvastatin prevented the impairment in endothelial-dependent vasorelaxation induced by H/R, and reduced by half the increase in ALT and AST (p<0.05). Transcriptomics showed a marked upregulation of genes related to inflammatory response after H/R in cirrhotic livers, but not in controls, and this was blunted by simvastatin. In conclusion, H/R aggravates liver microvascular dysfunction in cirrhosis, and upregulates liver inflammatory pathways. This does not occur in control livers. Simvastatin prevented H/R-induced liver endothelial dysfunction, and attenuated liver injury and liver inflammatory response, suggesting that it might have potential for protecting the cirrhotic liver during bleeding complications.
2016-12-22 | GSE84178 | GEO
Project description:The mammalian liver possesses a remarkable regenerative ability. 1) The 'oval cell' response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. 2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). We establish a long-term 3D organoid culture system from mouse and human fetal/pediatric/adult hepatocytes that retain key morphological and functional features of hepatocytes fate. We report the mRNA and single cell sequencing of Hep-Orgs from different donors in different passages. We compared Hep-Orgs with primary hepatocytes, proliferative hepatocytes or Chol-Orgs derived from Epcam+ biliary cells. By analyzing, we determine similar gene expression profile of Hep-Orgs with primary hepatocytes and make genes lists distinguished with undamaged hepatocytes as well. We find the Hep-Orgs resemble proliferative damage-response of hepatocytes after partial hepatectomy while Chol-Orgs express high cholangiocytes markers. The sequencing data constitutes a valuable resource to understand liver organoids especially Hep-Orgs.
2018-11-29 | GSE111301 | GEO
Project description:Cirrhosis and cancers of the upper digestive tract, colorectal and ENT share common risk factors. Liver cirrhosis can change the elimination of cancer drugs.
Precise data on management and outcome of patients with liver cirrhosis undergoing chemotherapy are lacking. Most patients have been excluded from clinical trials evaluating conventional therapies.
The study of tolerance, side effects, and outcome in patients with cirrhosis could help improve chemotherapy management for better tolerance and efficacy.
The main objective is to estimate the frequency of liver cirrhosis among patients evaluated in CPR for ENT, upper digestive or colorectal cancer.
Secondary objective includes the evaluation ofthe impact of cirrhosis on the management of chemotherapy by comparing cirrhotic patients’ outcomes with a control group of matched non-cirrhotic patients.
| 2323209 | ecrin-mdr-crc
Project description:The Wnt target gene Lgr5 marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A 3D culture system allows long-term clonal expansion of single Lgr5+ stem cells into transplantable organoids that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist Rspo, the recently discovered ligand of Lgr5. Here we show that Lgr5-LacZ is not expressed in healthy adult liver, yet that small Lgr5-LacZ+ cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signaling. As shown by lineage tracing using a novel Lgr5-ires-CreERT2 knock-in allele, damage-induced Lgr5+ cells generate hepatocytes and bile ducts in vivo. Single Lgr5+ cells from damaged liver can be clonally expanded as organoids in Rspo1-based culture medium over multiple months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into FAH-/- mice. These findings imply that previous findings on Lgr5+ stem cells in actively self-renewing tissues extend to damage-induced stem cells in a tissue with a low rate of spontaneous self-renewal. We first generated arrays from multiple wildtype tissues including muscle, white adipose tissues, brown adipose tissues, liver and pancreas. Then we generated arrays from liver derived cultures maintained in different conditions, and compared the expression profile with the corresponding parental tissues and other non-related tissues.
2013-01-28 | E-GEOD-32210 | biostudies-arrayexpress