This SuperSeries is composed of the SubSeries listed below.
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
View SamplesUtilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease. We characterized genome-wide expression profiles of hypomorhpic C. elegans mutants in nuclear-encoded subunits of respiratory chain complexes I, II and III.
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
View SamplesUtilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease. We characterized genome-wide expression profiles of hypomorphic C. ele
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
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 SamplesKeratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Long non-coding RNAs (lncRNAs) are involved in various biological processes, and their role in cancer progression is emerging. Whole transcriptome analysis of cSCC cells (n=8) and normal human epidermal keratinocytes (NHEKs, n=4) revealed overexpression of long intergenic ncRNA (LINC00162) in cSCC cells (GSE66412). We wanted to futher study the RNA expression profile of LINC00162 knockdown cSCC cells. Based on our observations, LINC00162 was named PICSAR (P38 Inhibited Cutaneous Squamous cell carcinoma Associated lincRNA). Overall design: RNA-Seq analysis of cSCC cells followed by siRNA-induced gene knockdown of lincRNA PICSAR. Total RNAs from negative control and PICSAR siRNA-treated cSCC cell lines (n=3) were extracted. The samples were sequenced using Illumina sequencing.
Long non-coding RNA PICSAR decreases adhesion and promotes migration of squamous carcinoma cells by downregulating α2β1 and α5β1 integrin expression.
No sample metadata fields
View SamplesThe global impact of DNA methylation on alternative splicing is largely unknown. Using a genome-wide approach in wild-type and methylation-deficient embryonic stem cells, we found that DNA methylation can act both as an enhancer and as a silencer of splicing, and affects the splicing of more than 20% of alternative exons. These exons are characterized by distinct genetic and epigenetic signatures. Alternative splicing regulation of a subset of these exons can be explained by Heterochromatin protein 1 (HP1), which silences or enhances exon recognition in a position-dependent manner. We constructed an experimental system using site-specific targeting of a methylated/unmethylated gene, and demonstrate a direct causal relationship between DNA methylation and alternative splicing. HP1 regulates this gene’s alternative splicing in a methylation-dependent manner by recruiting splicing factors to its methylated form. Our results demonstrate DNA methylation''s significant global influence on mRNA splicing, and identify a specific mechanism of splicing regulation mediated by HP1. Overall design: BS-seq on WT mouse ES cells (2 replicates), MNase-seq on WT and TKO cells (3 replicates), mRNA-seq on WT and TKO cells as well as HP1 knock-down cells (2 replicates for each sample)
HP1 is involved in regulating the global impact of DNA methylation on alternative splicing.
No sample metadata fields
View SamplesPurpose: To investigate the effects of T cell-derived cytokines on gene and protein expression of chemokines in a human RPE cell line (ARPE-19).
Chemokine expression in retinal pigment epithelial ARPE-19 cells in response to coculture with activated T cells.
Specimen part, Cell line
View SamplesPurpose: The complement system is closely linked to the pathogenesis of age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE), and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice.
Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.
Specimen part
View SamplesPurpose: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.
Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis.
Specimen part, Cell line
View SamplesWe used microarrays to identify the gene expression changes after SET knockdown in ESCs and 4 day RA differentiated ESCs
Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.
Specimen part
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