Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103347 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Focal nodular hyperplasias (FNHs) are benign liver lesions considered to be a hyperplastic response to increased blood flow in otherwise normal liver. In contrast, FNH-like nodules occur in cirrhotic liver but share similar histopathological features. To better understand the pathophysiology of FNH, we performed a transcriptomic analysis. Methods: Affymetrix and cDNA microarrays were used to compare gene expression in eight FNHs with that in tissue from six normal livers. Selected genes were validated with quantitative RT-PCR in 70 benign liver tumors including adenomas and cirrhotic and FNH-like lesions. Results: Among the deregulated genes in FNHs, 19 were physiologically zonated in the normal liver lobule. All six periveinous genes were up-regulated in FNH, whereas 13 genes normally expressed in the periportal area were down-regulated. Immunohistochemistry revealed that glutamine synthetase was markedly overexpressed, forming anastomosed areas usually centered on visible veins. ß-catenin mRNA was slightly but significantly overexpressed, as were several known ß-catenin target genes. Moreover, activated hypophosphorylated ß-catenin protein accumulated in FNH in the absence of activating mutations. These results suggest zonated activation of the ß-catenin pathway specifically in FNH, whereas the other benign hepatocellular tumors, including FNH-like lesions, demonstrated an entirely different pattern of ß-catenin expression. Conclusions: In FNH, increased expression of the ß-catenin pathway was restricted to enlarged periveinous areas, which may explain the slight polyclonal over-proliferation of hepatocytes at the origin of the lesion. FNH-like nodules may have a different pathogenetic origin. Keywords: Disease state analysis
2008-06-18 | GSE9536 | GEO
Project description:We define a pathogenic role for a ß-catenin-activated genetic pathway in murine renal dysplasia. Cre-mediated stabilization of ß-catenin in the ureteric cell lineage prior to the onset of kidney development increased ß-catenin levels and caused renal aplasia or severe hypodysplasia. A genome-wide analysis of mRNA expression in dysplastic tissue identified down-regulation of genes required for ureteric branching and up regulation of Tgfß2 and Dkk1. Hoxb7-Cre:EGFP mice ( Zhao, et al. (2004) Dev Biol 276:403-415) were crossed with mice containing loxP sites flanking exon 3 of the ß-catenin allele (ß-catdelta3/delta3) (Harada,et al. (2002) Cancer Res 62:1971-1977) to generate ß-catenin gain-of-function mutant mice specific to the uteric bud, termed ß-catGOF-UB .Eighteen ß-catGOF-UB mutant kidneys and 9 WT kidneys were micro-dissected at E12.5. Mutant kidneys were divided into three random pools (n=3) consisting of 6 kidneys each and mRNA expression assessed by microarray.
2011-03-28 | E-GEOD-20325 | biostudies-arrayexpress
Project description:Secondary hyperparathyroidism is well known complication manifested in end-stage renal disease (ESRD). Both nodular and diffuse parathyreoid hyperplasia occur in ESRD patients. Distinct molecular mechanisms involved in parathyreoid hyperplasia remain poorly understood. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients as compared to transplant cohort and primary hyperparathyreoidism, therefore further studies were performed in hemodialysis patints only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyreoid hyperplasia revealed highly significant differences in GO terms and KEGG database in ribosome structure (p=3.70-18). Next, RT-qPCR validation of microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF, p<0.001), calcyclin binding protein (CACYBP, p<0.05) and exocyst complex component 8 (EXOC8, p<0.05) and lower expression of peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1, p<0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed RANGRF and PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. Higher expression of genes associated with ribosomal structure and function underline extended translation mechanisms involved in parathyreoid nodular formation in long-term hemodialysis treated patients. Parathyroid tissue obtained from ESRD hyperparathyroidism patients who had undergone parathyroidectomy were used for transcriptome screening (Illumina HumanHT-12 v4.0 Expression BeadChips) and subsequently for discriminatory gene analysis, pathway mapping and gene-annotation enrichment analyses. Results were verified on enlarged group of hemodialysis patients with nodular (n=20) and diffuse (n=20) hyperplasia using RT-qPCR method.
2015-12-12 | E-GEOD-75886 | biostudies-arrayexpress
Project description:Analysis of the transcriptome of ß-catenin flox/- mES cells in comparison with ß-catenin null mES cells or ß-catenin null mES cells stably transfected with an E-cadherin-?-catenin fusion protein. Expression assay was performed using the Affymetrix GeneChip Mouse Gene 1.0 ST array. The experiment includes ß-catenin flox/-, ß-catenin null and ß-catenin null E? mouse embryonic stem cells with three biological replicates for each sample.
2013-05-03 | E-GEOD-44543 | biostudies-arrayexpress
Project description:ß-catenin is part of the cell-cell adhesion complex, where it plays a structural role but is also the key effector of the Wnt pathway, where it is endowed with a transcriptional regulatory activity. Oncogenic mutations of ß-catenin are present in about one third of hepatocellular carcinoma. In most tumors, ß-catenin mutations are heterozygous meaning that mutated and wild-type proteins co-exist in tumor cells. We address here the interplay between wild-type and mutated ß-catenins in liver tumor cells. We have designed a RNA interference strategy in HepG2 cells that allows uncoupling of the two functions of ß-catenin in the same cellular background: nuclear/transcriptional activity, a function almost exclusively mediated by the mutated ß-catenin, and membrane/structural activity, which is mediated by the degradable WT ß-catenin.
2021-01-22 | GSE144107 | GEO
Project description:Hepatocarcinogenesis is a multi-stage process in which precursor lesions progress into early hepatocellular carcinomas (eHCC) by sequential accumulation of multiple genetic and epigenetic alterations. To decode the molecular events during early stages of liver carcinogenesis, we performed gene expression profiling on cirrhotic (regenerative) and dysplastic nodules (DN) as well as eHCC. Although considerable heterogeneity was observed at the regenerative and dysplastic stages, clear differences were detected between DN and eHCC which included 460 differentially expressed genes. Functional analysis of the significant gene set identified the MYC oncogene as a plausible driver gene for malignant conversion of the dysplastic nodules. In addition, gene set enrichment analysis (GSEA) revealed a remarkable enrichment of MYC up-regulated gene set in eHCC versus dysplasia. Presence of the MYC signature significantly correlated with increased expression of CSN5 as well as with the higher overall transcription rate of genes located in the 8q chromosome region. Furthermore, a classifier constructed from MYC target genes could robustly discriminate eHCC from high- and low-grade dysplastic nodules. In conclusion, our study identified unique expression patterns associated with the transition of high-grade dysplastic nodules to early HCC and demonstrated that activation of the MYC transcription signature is critical for the malignant conversion of pre-neoplastic liver lesions. Samples from forty-nine nodular liver lesions including 24 regenerative (cirrhotic) nodules (CN), 3 low-grade (LGDN), 12 high-grade dysplastic nodules (HGDN) and 10 early hepatocellular carcinomas (Early HCC) were used. The Human Operon V2 oligonucleotide library containing 22K features representing expressed sequences was printed to glass arrays in the Advanced Technology Center (National Cancer Institute, Gaithersburg, MD). The aRNA probes were fragmented and hybridized to the microarray slides following the standard procedures. All samples were hybridized against a common amplified reference RNA pooled from normal liver samples. Experimental duplicates were prepared following a reverse-flour design.
2010-05-15 | E-GEOD-12443 | biostudies-arrayexpress
Project description:We define a pathogenic role for a ß-catenin-activated genetic pathway in murine renal dysplasia. Cre-mediated stabilization of ß-catenin in the ureteric cell lineage prior to the onset of kidney development increased ß-catenin levels and caused renal aplasia or severe hypodysplasia. A genome-wide analysis of mRNA expression in dysplastic tissue identified down-regulation of genes required for ureteric branching and up regulation of Tgfß2 and Dkk1.
2011-03-28 | GSE20325 | GEO
Project description:We compared transcriptomic profiles of 23 ICC tumor specimens to hepatocellular carcinoma (HCC) specimens using Affymetrix mRNA array and the miRNA array platforms to search for unique gene signatures linked to patient prognosis. ICC and HCC share common stem-like molecular characteristics and stem-like tumor features associated with poor prognosis. Gene expression profiling of 16 intrahepatic cholangiocarcinoma (ICC), 7 mixed type of combined HCC and ICC (CHC), 2 Hepatic Adenoma, 5 Focal Nodular Hyperplasia, and 7 Non-Tumor Tissues were performed.
2012-09-28 | E-GEOD-32879 | biostudies-arrayexpress
Project description:Secondary hyperparathyroidism is well known complication manifested in end-stage renal disease (ESRD). Both nodular and diffuse parathyreoid hyperplasia occur in ESRD patients. Distinct molecular mechanisms involved in parathyreoid hyperplasia remain poorly understood. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients as compared to transplant cohort and primary hyperparathyreoidism, therefore further studies were performed in hemodialysis patints only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyreoid hyperplasia revealed highly significant differences in GO terms and KEGG database in ribosome structure (p=3.70-18). Next, RT-qPCR validation of microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF, p<0.001), calcyclin binding protein (CACYBP, p<0.05) and exocyst complex component 8 (EXOC8, p<0.05) and lower expression of peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1, p<0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed RANGRF and PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. Higher expression of genes associated with ribosomal structure and function underline extended translation mechanisms involved in parathyreoid nodular formation in long-term hemodialysis treated patients.
2015-12-12 | GSE75886 | GEO
Project description:Context dependent molecular cues shape the formation of the cerebral vascular network and the function of the blood-brain barrier (BBB). The Wnt/ß-catenin pathway is orchestrating CNS vascular development, but downstream mediators have not been characterized. Here we generated an endothelial cell-specific R26-Axin1 overexpression (AOE) mouse model to inhibit Wnt/ß-catenin signaling. In AOE mice we discovered that blockade of Wnt/ß-catenin pathway leads to premature regression and remodeling without compromising BBB integrity. Importantly, by comparing transcriptomes of endothelial cells from wildtype and AOE mice, we identified ADAMTSL2 as a novel Wnt/ß-catenin-induced, secreted factor, important for stabilizing the BBB during development. Zebrafish loss-of-function and gain-of-function models, further demonstrated that ADAMTSL2 is crucial for normal vascular development and could rescue vascular phenotypes in AOE zebrafish brains. In conclusion, the studies presented here reveal a hitherto unrecognized role of ADAMTSL2 as an endothelial cell-specific mediator of Wnt/ß-catenin signaling during CNS vascular development and BBB-formation.
2019-02-22 | GSE66848 | GEO