In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing the surrounding vasculature network. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines responded strikingly different to hypoxia. We demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response. Overall design: 16 paired-end samples in total: 4 different cell lines sequenced in duplicate across 2 conditions each.
Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.
Specimen part, Treatment, Subject
View SamplesDifferent combinations of Endoglin tissue specific enhancers define hemangioblast and hemogenic endothelium cell fractions Overall design: We generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by tissue specific promoter/enhancer combinations of Endoglin (ENG). The Eng promoter (P) when combined with the -8/+7/+9kb enhancers targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8kb enhancer targeted TIE2+/c-KIT+/CD41- HE cells that were enriched for hematopoietic potential. These cell fractions were isolated and their transcriptomes profiled by RNA-seq.
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.
Subject
View SamplesIn the urinary tract, smooth muscle (SM) is present in the renal pelvis, the ureter, the bladder and the urethra and plays a crucial role in the functional and structural integrity of these organs. In Tshz3 mutant ureters the myogenic program is not activated in the proximal region due to the absence of expression of myocardin (Myocd), a key regulator of SM differentiation. We set out to characterize TSHZ3-dependent mechanisms that participate to the process of ureteric smooth muscle cells (SMC) differentiation.
The tiptop/teashirt genes regulate cell differentiation and renal physiology in Drosophila.
Specimen part
View SamplesOpi10 is the S. pombe homolog of human Hikeshi, which imports Hsp70s into the nucei during the heat shock.
The Schizosaccharomyces pombe Hikeshi/Opi10 protein has similar biochemical functions to its human homolog but acts in different physiological contexts.
No sample metadata fields
View SamplesGangliogliomas, the most frequent neoplasms in patients with pharmacoresistant focal epilepsies, are characterized by histological combinations of glial and dysplastic neuronal elements, a highly differentiated phenotype and rare gene mutations.<br></br><br></br>Here, we have used discrete microdissected ganglioglioma and adjacent control brain tissue obtained from the neurosurgical access to the tumour of identical patients (n = 6) carefully matched for equivalent glial and neuronal elements in an amount sufficient for oligonucleotide microarray hybridization without repetitive amplification. Multivariate statistical analysis identified a rich profile of genes with altered expression in gangliogliomas.
Array analysis of epilepsy-associated gangliogliomas reveals expression patterns related to aberrant development of neuronal precursors.
Sex, Specimen part, Disease, Subject
View SamplesMIST1 is a bHLH transcription factor that is necessary for the maturation of gastric zymogenic cells as they differentiate from their precursor mucous neck cells. In this experiment, mucous neck cells and zymogenic cells of normal, adult C57BL/6 and MIST1 knockout mice were laser-capture microdissected in order to determine MIST1-dependent, zymogenic cell specific gene expression.
The ubiquitin ligase Mindbomb 1 coordinates gastrointestinal secretory cell maturation.
Specimen part
View SamplesNPTX1 is a key inducer of neural lineages from the human ESC.
NPTX1 regulates neural lineage specification from human pluripotent stem cells.
Cell line, Time
View SamplesCeliac disease (CeD) is an intestinal immune-mediated disorder caused by gluten ingestion in genetically predisposed subjects. CeD is characterized by villous atrophy, altered intestinal permeability, crypt hyperplasia and innate and adaptive immune response. This study aimed to develop and validate the use of intestinal organoids from celiac patients to study CeD. A repository of organoids from duodenum of non-celiac and celiac patients was generated and characterized accordingly to standard procedures. RNA-seq analysis was employed to study the global gene expression program of CeD (n=3) and non-CeD (n=3) organoids sets. While the three celiac derived organoids shared similar transcriptional signatures the NC samples set appeared more heterogeneous. We found 486 genes differentially expressed between the two groups. Of them, 299 genes were downregulated (FC<2; FDR<0.05) and 187 were upregulated in CeD (FC >2; FDR<0.05). We observed CeD organoids had significantly altered expression of genes associated with barrier function, innate immunity, and stem cell function. Overall design: mRNA profiles of 3 non-celiac healthy controls and 3 celiac organoids derived from duodenal biopsies.
Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease.
Specimen part, Disease, Subject
View SamplesInflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. It is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides. We compared transcriptomes of human vaginal cells (Vk2/E6E7) treated with well-characterized pro-inflammatory (PIC) and non-inflammatory (NIC) compounds. Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by all PICs compared to NICs, thus distinguishing between these two groups.
Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.
Specimen part, Cell line
View SamplesThe clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversial discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 572 de novo AML with wildtype CEBPA and normal karyotype. The distal promoter was methylated in 54/572 cases (9.41%) whereas proximal PM was never detected. Methylation of the core promoter was detected in only 8 of 326 cases (2.45%) and thus seems to be a rare event in AML. There was no correlation between CEBPA distal PM, age, sex, white blood cell (WBC) count or Hb levels at diagnosis. We also were not able to detect a significant correlation between the presence of CEBPA distal PM and molecular mutations such as FLT3-ITD, NPM1, AML1, MLL-PTD and IDH1. Solely the frequency of IDH2R140 mutations was significantly reduced in CEBPA distal PM positive compared to CEBPA distal PM negative cases (p=0.01). Furthermore, analysis of CEBPA mRNA expression level revealed no difference between CEBPA distal PM positive and CEBPA distal PM negative cases, suggesting that CEBPA distal PM has no influence on CEBPA expression. CEBPA distal PM did not show impact on overall survival (OS), event free survival (EFS) or incidence of relapse. Also when other mutations were taken into regard no prognostic impact of CEBPA distal PM could be shown. In contrast, a distinct expression profile of CEBPA distal PM positive cases compared to CEBPA mutated and CEBPA distal PM negative cases was observed. In addition, a significantly higher frequency of CEBPA distal PM was detected in RUNX1-RUNX1T1 positive AML compared to the CEBPA witdtype cases. We conclude that the presence of aberrant CEBPA PM has no clinical relevance and is therefore a negligible prognostic marker in de novo AML with normal karyotype.
Frequency and prognostic impact of CEBPA proximal, distal and core promoter methylation in normal karyotype AML: a study on 623 cases.
Disease
View Samples