Primary liver tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and a group of rare tumours exhibiting biliary and hepatocytic differentiation called combined hepatocholangiocarcinomas (cHCC-CC). To better define this latter group, we take advantage of a series of these tumours based on their morphological characteristics and we performed transcriptional analysis allowing thereafter global comparison with published data. We show that most cHCC-CCs express progenitor cell traits, are committed to biliary lineage and are mainly associated to the activation of Wnt/beta-catenin and TGFbeta signalling pathways. Wnt/beta-catenin pathway activation in cHCC-CC is evidenced by the expression of both its direct targets such as LEF1 and EPCAM. In addition, extracellular matrix (ECM) genes and ECM-remodelling genes which are upon the control of TGF profibrotic program were found up-regulated in cHCC-CC. Interestingly, we show that CC and most cHCC-CC share characteristics associated to a subtype of poorly differentiated HCC suggesting that these tumours could originate from a stem/progenitor cell. The plasticity of these cells may explain the phenotypical heterogeneity of these tumors with the maintenance of some hepatocellular differentiation features such as albumin expression. Interestingly, this is shared by at least one third of CC, raising the hypothesis of a potential continuum between CC, cHCC-CC and poorly differentiated HCC.
Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFβ signaling pathways.
Sex, Specimen part
View SamplesMouse liver tumors (T) and non tumoral adjacent livers (NT) sorted from mice knock out for Axin1 gene specifically in the hepatocytes . 3 mice of the brother hood non deleted for Axin1 were used as controls (WT)
AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation.
Sex, Age, Specimen part
View SamplesTranscriptom analysis of microdissect adrenal medulla after 8 weeks of cardiac pressure overload caused by transverse aortic constriction.
Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis.
Sex
View SamplesCharacterization of genes associated with adipose tissue is key to understanding the pathogenesis of obesity and developing treatments for this disorder. Differential gene expression in the adipose tissue has been described in adulthood but none studies have been developed on childhood. The purpose of this study was to compare gene expression in omental adipose tissue from obese prepubertal and normal weight children. We selected 5 obese (BMI adjusted for age and sex z score >2) and 6 normal weight children. RNA was extracted from omental adipose tissue biopsies and cRNA was hybridizated on the human genome U133 Plus 2.0 Arrays (Affymetrix). Microarray experiments were performed for each sample, and selected group of gene expression values were confirmed with real-time RT-PCR in 10 obese and 10 normal weigth prepubertal children. 1276 genes were found to be differentially expressed at P<0.05. Of those differential genes, 201 were upregulated (Fc>2) and 42 were downregulated (Fc<-2). Genes involved in metabolic and signalling pathways were altered in childhood obesity.
Genome-wide expression in visceral adipose tissue from obese prepubertal children.
Sex, Age, Specimen part
View SamplesTranscriptom analysis of stellate sympathetic ganglia after 8 weeks of cardiac pressure overload caused by transverse aortic constriction.
Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload.
Sex
View SamplesCardiac hypertrophy is associated with growth and functional changes of cardiomyocytes,including mitochondrial alterations, but the latter are still poorly understood. Here we investigated mitochondrial function and dynamic localization in neonatal rat ventricular cardiomyocytes (NRVCs) stimulated with insulin like growth factor 1 (IGF1) or phenylephrine (PE), mimicking physiological and pathological hypertrophic responses,respectively.
Hypertrophy induced KIF5B controls mitochondrial localization and function in neonatal rat cardiomyocytes.
Specimen part
View SamplesTo determine the physiological targets of the NELF complex, and provide insight into the mechanism of NELF activity in vivo.
NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly.
No sample metadata fields
View Samplesalpha2-adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the three alpha2-adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the alpha2-adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in alpha2-adrenoceptor genes.
Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice.
No sample metadata fields
View SamplesDevelopment requires the cooperation of tissue-specific and ubiquitously expressed transcription factors, such as Sp-family members. However, the molecular details of how ubiquitous factors participate in developmental processes are still unclear. We previously showed that during the differentiation of embryonic stem cells lacking Sp1 DNA binding activity (Sp1deltaDBD/deltaDBD cells), early blood progenitors are formed. However, gene expression during differentiation becomes progressively deregulated and terminal differentiation is severely compromised. Here we studied the cooperation of Sp1 and its closest paralogue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. Sp3 cooperates with Sp1deltaDBD/deltaDBD but is unable to support hematopoiesis in the complete absence of Sp1. Using single cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin bi nding of Sp1 is required to maintain robust differentiation trajectories. Overall design: RNA-Seq in ESC, Flk, HE1, HE2 and progenitor cells with WT, Sp1deltaDBD or Sp3KO
Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors.
Specimen part, Cell line, Subject
View SamplesFN044, FN211, FN242 and FN303 are the fast neutron generated mutants in cv. Steptoe background. These 4 mutants have lesion mimic phenotype and increase disease resistance to stem rust. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, ling zhang. The equivalent experiment is BB54 at PLEXdb.]
A cation/proton-exchanging protein is a candidate for the barley NecS1 gene controlling necrosis and enhanced defense response to stem rust.
Specimen part
View Samples