Integrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Specimen part
View SamplesThe 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 SamplesInflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
No sample metadata fields
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 SamplesGene expression in adult male and female mouse liver was assayed by RNA-seq, as part of a study on hepatic lincRNAs. Overall design: Total liver RNA was prepared from 12 individual male and 12 individual female mice. Four independent pools, comprised of RNA isolated from 6 individual male or female livers (2 pooled biological replicates for each sex) were then 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 male and female mouse liver was assayed by RNA-seq, as part of a study on chromatin states in male and female mouse and their role in sex-biased liver gene expression (A Sugathan and DJ Waxman (2013) Mol Cell Biol. 33:3594-3610. doi: 10.1128/MCB.00280-13). Overall design: Total liver RNA was prepared from 12 individual male and 12 individual female mice. Four RNA pools, comprised of RNA isolated from 6 individual male or female livers (2 pooled biological replicates for each sex) were then prepared and used for RNA-seq.
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
Sex, Age, Cell line, Subject
View SamplesGene expression in adult male and female mouse liver was analyzed based on nuclear RNA-seq, as part of a study on hepatic lincRNAs. Overall design: Nuclear liver RNA was prepared from 6 individual male and 6 individual female mice. Pools comprised of RNA isolated from 6 individual male or female livers (1 pool of 6 biological replicates for each sex) were then prepared and used for strand-specific RNA-seq.
Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone.
No sample metadata fields
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 Samples