The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion: Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer.
Liver regeneration signature in hepatitis B virus (HBV)-associated acute liver failure identified by gene expression profiling.
Specimen part, Disease, Disease stage, Subject
View SamplesExpression analysis of migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow
Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration.
Specimen part
View SamplesTo investigate the role of viral and host factors in HDV-associated HCC we carried out an integrated clinicopathological and gene expression study of tissue specimens and laser microdissected hepatocytes obtained at the time of liver transplantation from livers with HDV-HCC, HDV-cirrhosis without HCC, HCV-HCC and HBV-HCC. References to GSM series of HDV and HBV livers, already deposited in GEO, are included in this series. Part of data of HCV livers are a re-analysis of GSE series GSE69715 and GSE78737, the re-analyzed GSM is indicated in the 'description' column and with a link at the bottom of the page.
Molecular Signature and Mechanisms of Hepatitis D Virus-Associated Hepatocellular Carcinoma.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.
Sex, Age, Specimen part, Cell line
View SamplesOur study identifies TACSTD2 as a novel regulator of two major HCV entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro.
Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.
Sex, Age, Specimen part
View SamplesTo investigate the role of viral and host factors in HDV-related HCC we analyzed the serum, tissue specimens and laser microdissected hepatocytes obtained at the time of liver transplantation from five patients with HDV-HCC. Livers of seven patients with HDV-cirrhosis without HCC were also analyzed. We carried out an integrated clinicopathological analysis and gene expression profiling,
Molecular Signature and Mechanisms of Hepatitis D Virus-Associated Hepatocellular Carcinoma.
Specimen part, Disease, Disease stage
View SamplesOur study identifies TACSTD2 as a novel regulator of two major HCV entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro.
Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.
Cell line
View SamplesGene expression in intact and hypophysectomized adult mouse liver was assayed by RNA-seq analysis of total liver RNA, as part of a study of growth hormone regulation of hepatic lincRNAs. Overall design: Eight independent pools: two intact males, two intact females, two hypophysectomized males and two hypophysectomized females, comprised of total RNA isolated from 3-5 individual livers / pool, were prepared and used for unstranded RNA-seq.
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
No sample metadata fields
View SamplesGene expression in adult male mouse liver was assayed by nuclear RNA-seq, as part of a study of hepatic lincRNAs. Overall design: Three independent pools, comprised of nuclear RNA isolated from 4 individual male livers per pool, were prepared and used for RNA-seq.
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
No sample metadata fields
View SamplesGene expression in adult female mouse liver was assayed by nuclear RNA-seq, as part of a study of hepatic lincRNAs. Overall design: Three independent pools, comprised of nuclear RNA isolated from 4 individual livers per pool, were prepared and used for unstranded RNA-seq.
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
No sample metadata fields
View Samples