Expression profiling of Ewing sarcoma samples in the frame of the CIT program from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net).
Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.
Sex, Age
View SamplesTo get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells.
Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThe opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThe opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThis study was designed to investigate the transcripts that are regulated by Twist1 in skin tymor epithelial cells in a p53-dependent and independent manner. To this aim, Tumor epithelial cells from primary mouse skin tumors of different genotypes were FACS sorted and analyzed by microarray.
Different levels of Twist1 regulate skin tumor initiation, stemness, and progression.
Specimen part, Treatment
View SamplesSerotonin in the mammary gland is known to regulate processes such as calcium homeostasis, tight junction permeability, and milk protein gene expression. The objective of this study was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate-limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 knock-out mice dams (serotonin deficient) and compared them to wild-type dams and also Tph1 deficient dams injected daily with 5-HTP. Mammary gland tissues were collected on day 10 of lactation and then analyzed by RNA sequencing. Overall design: Genome-wide gene expression profiles of 12 mouse mammary gland samples were evaluated using RNA sequencing; these 12 samples belong to wild-type dams (WT; n = 4), Tryptophan hydroxylase (Tph1) knock-out dams (KO; Tph1 deficient; n = 4), and Tph1 deficient dams injected daily with 5-HTP (RC; n = 4). Mammary tissues were collected on day 10 of lactation and then underwent RNA extraction, library generation, and subsequent sequencing.
Transcriptomic Analysis of the Mouse Mammary Gland Reveals New Insights for the Role of Serotonin in Lactation.
No sample metadata fields
View SamplesTranscriptional profile of control and VEGF overexpressing FACS-isolated CD34+ Cancer stem cells from DMBA/TPA induced skin tumours
A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours.
No sample metadata fields
View SamplesBasal cell carcinoma initiating cells undergo profound and rapid reprogramming into embryonic hair follicle progenitor like fate upon SmoM2 expression. Activation of Wnt/-catenin signaling pathways is required in a cell autonomous manner for the reprogramming of adult IFE progenitors into EHFP-like fate as well as for tumor initiation.
Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.
Specimen part
View SamplesCancer stem cells (CSCs) have been reported in various cancers including skin squamous cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here, we found that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells (SCs), was the most upregulated transcription factor in CSCs of squamous skin tumours. Sox2 is absent in normal epidermis and begins to be expressed in the vast majority of mouse and human pre-neoplastic skin tumours and continues to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In contrast to other SCCs, in which Sox2 is frequently genetically amplified, the expression of Sox2 in mouse and human skin SCCs is transcriptionally regulated. Conditional deletion of Sox2 in the mouse epidermis dramatically decreases skin tumour formation following chemical induced carcinogenesis. Using Sox2-GFP knockin mice, we showed that Sox2 expressing cells in invasive SCC are greatly enriched in tumour propagating cells (TPCs) that further increase upon serial transplantations. Lineage ablation of Sox2 expressing cells within primary benign and malignant SCCs leads to tumour regression, consistent with the critical role of Sox2 expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing skin papilloma and SCC leads to their regression and decreases their ability to be propagated upon transplantation into immunodeficient mice, supporting the essential role of Sox2 in regulating CSC functions. Transcriptional profiling of Sox2-GFP expressing CSC and upon Sox2 deletion uncovered a gene network regulated by Sox2 in primary tumour cells in vivo. Chromatin immunoprecipitation identified several direct Sox2 target genes controlling tumour stemness, survival, proliferation, adhesion, invasion, and paraneoplastic syndrome. Altogether, our study demonstrates that Sox2, by marking and regulating the functions of skin tumour initiating cells and CSCs, establishes a continuum between tumour initiation and progression in primary skin tumours.
SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma.
No sample metadata fields
View Samples