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SRP045611
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2500
Description
Purpose: We identified KPC1 as the ubiquitin ligase that binds to the p105 precursor of NF-kB, ubiquitinates it and mediates its proteasomal processing to generate the p50 active subunit of the transcription factor. Using U87-MG human glioblastoma xenografts, we observed that overexpression of KPC1 results in strong inhibition of tumor growth mediated via excessive generation of p50.The goal of this RNASeq study was to analyze the profile of gene expression in xenografts overexpressing control (V0), KPC1 or p50 vectors, and to further understand how the altered gene expression patterns can explain the tumor suppressive effect we observed. Results:Transcript analysis of U87-MG xenografts overexpressing control (V0), KPC1 or p50 vector mapped to the human genome revealed: • A strong similarity between overexpression of p50 and KPC1 (correlation of 0.51, p-value<10-300 ) • A specific signature of NF-kB targets [21 of the consistently changed genes are known to be regulated by NF-kB (p-value<3.4×10-9 )] • A significant (p-value<1.4×10-18) increase in the expression of 40 tumor suppressor genes, with no significant change in other classes. • A significant down regulation of a cluster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB. Overall design: Exponentially growing U87-MG cells were stably transfected with an empty vector (V0) or vectors coding for Myc-KPC1 or Flag-p50. Cells were dissociated with trypsin, washed with PBS, and brought to a concentration of 50×10^6 cells/ml. Cell suspension (5×10^6/0.1 ml) was inoculated subcutaneously at the right flank of 7-weeks old male Balb/C nude mice (n=7). Following 21 days, mRNA from U87-MG xenografts was isolated using an RNA purification kit, and analyzed using the Illumina HiSeq 2500 sequencer. The RNASeq analysis experiment was repeated twice independently. Run1 included a total of 7 samples. Samples 1-3 were isolated from V0 – control tumors (3 different tumors), samples 4-5 were isolated from KPC1-expressing tumors (2 different pools of 3 tumors each due to small tumor size), and samples 6-7 were isolated from p50-expressing tumors for (2 different pools of 2-3 tumors each, due to very small tumor size). Run2 included a total of 5 samples. Samples 8-10 were isolated from V0 (control) tumors (3 different tumors), samples 11-12 were isolated from KPC1 tumors (2 different pools of 3 tumors each due to small tumor size). Several repeated attempts to extract RNA from the p50-expressing tumors did not yield any results, as the tumors were miniscule.
Publication Title
KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
Melanoma is a highly aggressive cancer with increasing incidence rates and a poor survival, particularly in patients with AJCC stage IV and advanced stage III. Deregulation of NF-kB is linked to different pathological states, including melanoma. To identify the involvement of NF-kB pathway regulation in melanoma progression, we manipulated NF-kB pathway activation and profiled gene expression using RNA-sequencing. Overall design: mRNA profiles of IM-0223 cells overexpressing KPC1 (KPC1) or control (V0) generated by deep sequencing using Illumina HiSeq 2500.
Publication Title
Epigenetic Regulation of KPC1 Ubiquitin Ligase Affects the NF-κB Pathway in Melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Goal: Identify genes that are differentially expressed in hyper-aggressive Bully line. We used wildtype Canton-S flies as control. We also explored the effect of developmental temperature on gene expression. Overall design: Total RNA were extracted from 6-day-old adult heads from Canton-S or Bully lines that were raised at 19C or 25C. A total of 4 samples were obtained. For each sample, 2 independent biological replicates were included.
Publication Title
Putative transmembrane transporter modulates higher-level aggression in <i>Drosophila</i>.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Even after decades of living in the same laboratory environment two Drosophila melanogaster strains originating from North America (Canton-S) and Central Russia (D18) demonstrate a few differentially expressed genes some of which may be important for local adaptation (e.g. genes responsible for insecticide resistance). Genes with different level of expression between Canton-S and D18 strains belong to important metabolic pathways, for instance energy metabolism, carbohydrate metabolic process, locomotion, body temperature rhythm regulation and tracheal network architecture.
Publication Title
Transcriptome analysis of <i>Drosophila melanogaster</i> laboratory strains of different geographical origin after long-term laboratory maintenance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identify early processes in carcinogenesis, we used an in vitro model, based on the initiating event in cervical cancer, human papillomavirus (HPV) transformation of keratinocytes. We compared gene expression in primary keratinocytes (K) and HPV16-transformed keratinocytes from early (E) and late (L) passages, and from benzo[a]pyrene treated L cells (BP). The transformed cells exhibit similar transcriptional changes to clinical cervical carcinoma. We revealed a contraction in expression of the apoptotic network during HF1 cell transformation, which affected the ability of L and BP cells to execute apoptosis, but did not lead to resistance to apoptotic stimuli. The contraction in the apoptotic machinery during the process of transformation was accompanied by a switch from apoptosis to necrosis in response to CDDP. The shrinkage of the pro- and anti-apoptotic networks appears to be part of a general contraction in the number of genes transcribed in L and BP cells. We also identified a large group of genes with induced expression, which are involved in cell metabolism and cell cycle, suggesting increased investment of the transformed cell in cellular proliferation. We hypothesize that the decrease in expression of many diverse pathways, including the pro- and anti-apoptotic networks, cuts the energy requirements for cell maintenance, allowing energy to be diverted towards rapid cell proliferation. This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis.
Publication Title
Shift from apoptotic to necrotic cell death during human papillomavirus-induced transformation of keratinocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
Publication Title
Identification of human cytotoxic ILC3s.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
Transcriptional dysregulation is an early feature of Huntington''s disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. Overall design: mRNA-seq in wild type and R6/2 cortex and striatum at 8 and 12 weeks.
Publication Title
Targeting H3K4 trimethylation in Huntington disease.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Arabidopsis thaliana
- 58 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Many flowering plants attract pollinators by offering a reward of floral nectar. Remarkably, the molecular events involved in the development of nectaries, the organs that produce nectar, as well as the synthesis and secretion of nectar itself, are poorly understood. Indeed, to date, no genes have been shown to directly affect the de novo production or quality of floral nectar. To address this gap in knowledge, the ATH1 Affymetrix GeneChip array was used to systematically investigate the Arabidopsis nectary transcriptome to identify genes and pathways potentially involved in nectar production. In this study, we identified a large number of genes differentially expressed between secretory lateral nectaries and non-secretory median nectary tissues, as well as between mature lateral nectaries (post-anthessis) and immature lateral nectary tissue (pre-anthesis).
Publication Title
Uncovering the Arabidopsis thaliana nectary transcriptome: investigation of differential gene expression in floral nectariferous tissues.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Many flowering plants attract pollinators by offering a reward of floral nectar. Remarkably, the molecular events involved in the development of nectaries, the organs that produce nectar, as well as the synthesis and secretion of nectar itself, are poorly understood. Indeed, to date, no genes have been shown to directly affect the de novo production or quality of floral nectar. To address this gap in knowledge, the ATH1 Affymetrix GeneChip array was used to systematically investigate the Arabidopsis nectary transcriptome to identify genes and pathways potentially involved in nectar production. In this study, we identified a large number of genes differentially expressed between secretory lateral nectaries and non-secretory median nectary tissues, as well as between mature lateral nectaries (post-anthessis) and immature lateral nectary tissue (pre-anthesis).
Publication Title
Uncovering the Arabidopsis thaliana nectary transcriptome: investigation of differential gene expression in floral nectariferous tissues.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A control vs. genetic knockout experiment aimed at determining what RNAs are upregulated or downregulated in e11.5 mouse proximal limb tissue lacking the Lmx1b gene. Because Lmx1b is required for dorsal-ventral patterning of the limb, this screen gives insight into what putative downstream targets of Lmx1b contribute to dorsal-ventral patterning.
Publication Title
Identification of genes controlled by LMX1B in the developing mouse limb bud.
Sample Metadata Fields
No sample metadata fields
View Samples