In this study we conducted transcriptomics analyses of: (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (n=3) and from healthy livers (n=2) and (ii) hepatic cell systems exposed to acetaminophen, including their respective vehicle controls. The investigated in vitro systems are: HepaRG cells, HepG2 cells and a novel human skinpostnatal stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC).
Gene expression data from acetaminophen-induced toxicity in human hepatic <i>in vitro</i> systems and clinical liver samples.
Specimen part, Disease stage, Cell line
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Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sex, Age, Specimen part
View SamplesPURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy.
Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sex, Age, Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFS>50months) versus bad outcome (OS<19months and DFS<7months). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with -catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis.
Molecular markers associated with outcome and metastasis in human pancreatic cancer.
Sex, Age, Specimen part, Disease stage
View SamplesTo evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.
Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma.
Specimen part
View SamplesPurpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival.
Human pancreatic cancer contains a side population expressing cancer stem cell-associated and prognostic genes.
Sex, Age, Specimen part, Disease stage
View SamplesLiver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence underlies this regenerative failure. In human acute liver disease, and murine models, p21-dependent hepatocellular senescence was proportionate to disease severity and was associated with impaired regeneration. In an acetaminophen injury model a transcriptional signature associated with the induction of paracrine senescence is observed within twenty four hours, and is followed by one of impaired proliferation. In genetic models of hepatocyte injury and senescence we observed transmission of senescence to local uninjured hepatocytes. Spread of senescence depended upon macrophage derived TGFß1 ligand. In acetaminophen poisoning inhibition of TGFß receptor 1 (TGFßR1) improved survival. TGFßR1 inhibition reduced senescence and enhanced liver regeneration even when delivered after the current therapeutic window. This mechanism, in which injury induced senescence impairs regeneration, is an attractive therapeutic target for acute liver failure. Overall design: RNA-seq analysis was performed on a total of 24 samples extracted from murine liver, post hepatic injury induced by acetaminophen administration. Transcriptional profiles were from replicate samples generated at defined timepoints - 12, 24, 36, 48 and 72 hours post injury. Replicate samples were generated from 4 individual animals sacrificed at each timepoint, and compared to a control cohort of 4 animals not subjected to acetaminophen treatment.
TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence.
Specimen part, Cell line, Subject, Time
View SamplesWe have analysed a family with an autosomal recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship.
Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy.
Sex, Specimen part
View SamplesAlthough host-parasitoid interactions are becoming well characterized at the organismal and cellular levels, much remains to be understood of the molecular bases for the host immune response and the parasitoids ability to defeat this immune response. Leptopilina boulardi and L. heterotoma, two closely related, highly infectious natural parasitoids of Drosophila melanogaster, appear to use very different infection strategies at the cellular level. Here, we further characterize cellular level differences in the infection characteristics of these two wasp species using newly derived, virulent inbred strains, and then use whole genome microarrays to compare the transcriptional response of Drosophila to each. While flies attacked by the melanogaster group specialist Leptopilina boulardi (strain Lb17) up-regulate numerous genes encoding proteolytic enzymes, components of the Toll and JAK/STAT pathways, and the melanization cascade as part of a combined cellular and humoral innate immune response, flies attacked by the generalist L. heterotoma (strain Lh14) do not appear to initiate an immune transcriptional response at the time points post-infection we assayed, perhaps due to the rapid venom-mediated lysis of host hemocytes (blood cells). Thus, the specialist parasitoid appears to invoke a full-blown immune response in the host, but suppresses and/or evades downstream components of this response. Given that activation of the host immune response likely depletes the energetic resources of the host, the specialists infection strategy seems relatively disadvantageous. However, we uncover the mechanism for one potentially important fitness tradeoff of the generalists highly immune suppressive infection strategy.
Contrasting infection strategies in generalist and specialist wasp parasitoids of Drosophila melanogaster.
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View SamplesWomen are born with millions of primordial follicles which gradually decrease with increasing age and this irreversible supply of follicles completely exhausts at menopause. The fertility capacity of women diminishes in parallel with aging. The mechanisms for reproductive aging are not fully understood. In our recent work we observed a decline in BRCA1 mediated DNA repair in aging rat primordial follicles. To further understand the age-related molecular changes, we performed microarray gene expression analysis using total RNA extracted from immature (1820 days) and aged (400450 days) rat primordial follicles. The results of current microarray study revealed that there were 1011 (>1.5 fold, p<0.05) genes differentially expressed between two groups in which 422 genes were up-regulated and 589 genes were down-regulated in aged rat primordial follicles compared to immature. The gene ontology and pathway analysis of differentially expressed genes revealed a critical biological function such as cell cycle, oocyte meiosis, chromosomal stability, transcriptional activity, DNA replication and DNA repair were affected by age and this considerable difference in gene expression profiles may have adverse influence on oocyte quality. Our data provide information on the processes that may contribute to aging and age-related decline in fertility.
Age-related changes in gene expression patterns of immature and aged rat primordial follicles.
Specimen part
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