Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs. Overall design: RNA-seq of tumors from central nervous system primitive neuroectodermal tumor (CNS PNET) animal model
Stabilization of HIF-1α and HIF-2α, up-regulation of MYCC and accumulation of stabilized p53 constitute hallmarks of CNS-PNET animal model.
Specimen part, Disease stage, Subject
View SamplesRhabdoid tumors (RT) are aggressive tumors characterized by genetic loss of SMARCB1 (SNF5, INI-1), a component of the SWI/SNF chromatin remodeling complex. No effective treatment is currently available. This study seeks to shed light on the SMARCB1-mediated pathogenesis of RT and to discover potential therapeutic targets. Global gene expression of 10 RT was compared with 12 cellular mesoblastic nephromas, 16 clear cell sarcomas of the kidney, and 15 Wilms tumors. 114 top genes were differentially expressed in RT (p<0.001, fold change >2 or <0.5). Among these were down-regulation of SMARCB1 and genes previously associated with SMARCB1 (ATP1B1, PTN, DOCK4, NQO1, PLOD1, PTP4A2, PTPRK). 28/114 top differentially expressed genes were involved with neural or neural crest development and were all sharply down-regulated. This was confirmed by Gene Set Enrichment Analysis (GSEA). Neural and neural crest stem cell marker proteins SOX10, ID3, CD133 and Musashi were negative by immunohistochemistry, whereas Nestin was positive. Decreased expression of CDKN1A, CDKN1B, CDKN1C, CDKN2A, and CCND1 was identified, while MYC-C was upregulated. GSEA of independent gene sets associated with bivalent histone modification and polycomb group targets in embryonic stem cells demonstrated significant negative enrichment in RT. Several differentially expressed genes were associated with tumor suppression, invasion and metastasis, including SPP1 (osteopontin), COL18A1 (endostatin), PTPRK, and DOCK4. We conclude that RTs arise within early progenitor cells during a critical developmental window in which loss of SMARCB1 directly results in repression of neural development, loss of cyclin dependent kinase inhibition, and trithorax/polycomb dysregulation.
Rhabdoid tumor: gene expression clues to pathogenesis and potential therapeutic targets.
No sample metadata fields
View SamplesThe gene expression patterns of favorable histology Wilms tumors (FHWT) that relapsed were compared with those that did not relapse using oligonucleotide arrays
Predicting relapse in favorable histology Wilms tumor using gene expression analysis: a report from the Renal Tumor Committee of the Children's Oncology Group.
No sample metadata fields
View SamplesThe goal of this study is to define biologically distinct subsets of Very Low Risk Wilms Tumors (VLRWT) using oligonucleotide arrays.
Subsets of very low risk Wilms tumor show distinctive gene expression, histologic, and clinical features.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.
Specimen part
View SamplesGene expression during spermatogenesis is highly variable and this differential pattern is very important for the successive culmination of different stages of the process, leading to production of the male gamete. Taking the time window of first wave of spermatogenesis, we did a microarray profiling of total testicular transcriptome in mouse and found several significant patterns of variable gene expression, forming upregulated and downregulated clusters among the three stages analyzed here.
Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.
Specimen part
View SamplesBud endodormancy induction response of two genotypes (Seyval a hybrid white wine grape and V. riparia, PI588259 a native north american species) was compared under long (15h) and short (13h) photoperiod. Three separate replicates (5 plants/replicate) were treated to generate paradormant (LD) and same aged endodormancy-induced (SD) buds for transcriptomic, proteomic and metabolomic analysis. Potted, spur-pruned two to six-year-old vines were removed from cold storage (Seyval 3-19-07; V. riparia 3/26/07) and grown under a LD (15 h) at 25/20 + 3C day/night temperatures (D/N). When vines reached 12-15 nodes (3-25-07) they were randomized into LD or SD treatments with 25/20 + 3C D/N in climate controlled greenhouses with automated photoperiod system (VRE Greenhouse Systems). Three replications (5 vines/replication) were harvested between 5/07-6/07 and then again in 5/08-6/08 for a total of six replications. All treatments are repeated at the same time every year and harvested at the same time of day each year to minimize biological noise. At 1, 3, 7, 14, 21, 28 and 42 days of LD and SD treatment, buds were harvested from nodes 3 to 12 of each separate replicate, immediately frozen in liquid nitrogen, and placed at -80C for future RNA, protein and metabolite extraction. These time points encompass early reversible phases as well as key time points during transition to irreversible endodormancy development. After photoperiod treatments and bud harvests, all pruned vines were returned to LD and monitored for bud endodormancy. The endodormant vines were identified after 28 days and moved to cold storage. The nondormant vines were allowed to grow again and induced into dormancy at a later date. Acknowledgement:This study was funded by NSF Grant DBI0604755 and funds from the South Dakota Agriculture Experiment Station. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Anne Fennell. The equivalent experiment is VV10 at PLEXdb.]
Differential floral development and gene expression in grapevines during long and short photoperiods suggests a role for floral genes in dormancy transitioning.
Age, Specimen part
View SamplesA major part of plant immune response is mediated by signaling pathways controlled by three hormnes, jasmonate, ethylene, and salicylate. The involvement of each of these hormone signaling pathways in Arabidopsis thaliana was investigated in response to infection of a necrotrophic fungal pathogen, A. brassicicola. Arabideopsis mutants deficient in these hormone signaling pathways were compared to wild type.
Arabidopsis PECTIN METHYLESTERASEs contribute to immunity against Pseudomonas syringae.
Specimen part
View SamplesPro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta/alpha (IL1beta/alpha) modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Interleukin-6 (IL6), also released during inflammation, affects transcriptional responses in primary chromaffin cells, and may coordinate immune and autonomic adrenomedullary responses via an autocrine mechanism, as TNFalpha itself strongly induces IL6 expression in chromaffin cells, which in turn express receptors responsive to IL6. We have examined the signaling mechanisms employed by IL6 to affect tyrosine hydroxylase (TH) enzymatic activation, and adrenomedullary gene transcription, in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine phosphorylation of signal transducer and activator of transcription 3 (STAT3), as do several other first messengers acting on the chromaffin cell, including histamine, nicotine and angiotensin II. IL6 uniquely activated tyrosine phosphorylation of STAT3. Consistent with a short-term ERK1/2 activation, IL6 treatment caused prompt regulation of TH phosphorylation, and up-regulation of genes encoding secreted proteins of the adrenal medulla including galanin, vasoactive intestinal peptide (VIP), gastrin releasing peptide (GRP) and parathyroid hormone-like hormone (PTHLH). We further examined the effects of IL6 treatment on the entire bovine chromaffin cell transcriptome. Of 90 genes up-regulated by IL6, only 16 of which are known targets of IL6 in the immune system. The remaining genes likely represent a combination of novel IL6/STAT3 targets, targets of ERK1/2 shared by other first messengers, and, potentially, IL6-dependent genes activated in a secondary cascade via transcription mediated by IL6-induced transcription factors, such as HIF-1alpha. Notably, genes induced by IL6 represent a cohort with a profile that includes both neuroendocrine-specific genes, including several that are activated by G-protein couple receptor (GPCR) signaling pathways initiated by histamine and pituitary adenylate cyclase-activating polypeptide (PACAP), and some transcripts also activated by cytokines including interferon-alpha (INFalpha and TNFalpha. These results suggest an integrative role for IL6 in overall fine-tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge in the adrenal medulla.
Interleukin-6-mediated signaling in adrenal medullary chromaffin cells.
Specimen part
View SamplesAndrogens are required for the development of normal prostate, and they are also linked to the development of prostate cancer.
Proteomic interrogation of androgen action in prostate cancer cells reveals roles of aminoacyl tRNA synthetases.
Specimen part, Cell line
View Samples