This SuperSeries is composed of the SubSeries listed below.
Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity.
Specimen part, Treatment
View SamplesConstitutively active MYC and reactivated telomerase often co-exist in cancers. While the reactivation of telomerase is thought to be essential for replicative immortality, MYC, in conjunction with co-factors, confers several growth advantages to cancer cells. However, it is unclear which co-factors sustain elevated MYC activity in tumors . Here, we identify TERT, the catalytic subunit of telomerase, as a novel regulator of MYC stability in cancers. Binding of TERT to MYC stabilizes its levels on chromatin, contributing to either activation or repression of its target genes. Mechanistically, TERT regulates MYC ubiquitination and stability, and this effect of TERT is independent of its role on telomeres. Genetic inhibition and knocking out of TERT phenocopied the loss of MYC, resulting in reduced disease burden of early- and late-stage MYC-driven murine lymphomas. Conversly, the ectopic expression of TERT could substitute for reduced MYC in these functions. Finally we show that TERT null mice, unlike Terc null mice, show delayed onset of MYC induced lymphomagenesis. Accordingly, inhibiting TERT function in primary human leukemia cells blocked the expression of MYC targets, while Terc depletion had no effects . Based on our data, we conclude that the re-expression of TERT, a direct MYC target in tumors, provides a feed-forward mechanism to potentiate MYC-dependent oncogenesis.
Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity.
Specimen part, Treatment
View SamplesPurpose: The Ikk2 maternal-zygotic mutants are the only vertebrates animals completely depleted globally of the Ikk2 function which is expected to block an activity of the canonical NFkB signaling pathway. Transcriptome profiling of embryos before the midblastula transition (MBT) and after MBT may provide a clean strategy to identify the NFkB target genes. Methods: Zebrafish lines were maintained under standard laboratory procedures. Results: Using an optimized data analysis workflow, we identified 54,276 transcripts in the embryos at 2 hours postfertilization (hpf) and 4 hpf. RNA-seq data confirmed lack of expression of a number of genes in the mutant both prior to and after the MBT, including genes linked to angiogenesis, skin development, cytokinesis, innate immunity and cytoskeletonT, and 4 of these were validated with qRT–PCR. M. add here if required. Conclusions: Our study represents the first detailed analysis of transcriptomes of vertebrates globally depleted of activity of Ikk2, with two biologic replicates, generated by RNA-seq technology.The data reported here should provide a framework for understanding of maternal and zygotic genes which expression is controlled by Ikk2 activity. Our results expands a list of transcripts which expression may be controlled by the canonical NFkB signaling. We conclude that RNA-seq based transcriptome characterization improves analysis of NFkB regulated genes. Overall design: Zebrafish Ikk2 mutants were obtained using zinc-finger nuclease-mediated mutagenesis. Some of the mutant homozygotic embryos grow into fertile adults able to produce embryos totally deplated of maternal and zygotic Ikk2.
Ikk2 regulates cytokinesis during vertebrate development.
No sample metadata fields
View SamplesWe performed microarray gene expression profiling in 16 T-ALL cell lines
Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesHere, we characterized the transcriptome of MCs under steady state, immunoglobulin E (IgE)-sensitized and anti-IgE-treated conditions. Overall design: MCs were left untreated or sensitized overnight with myeloma-IgE (0.5 µg/ml) and treated with anti-IgE (1 µg/ml) for 2h. RNA was isolated with Trizol and RNeasy columns and RNA-seq was performed.
Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases.
Specimen part, Subject
View SamplesThe RUNX genes encode for transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here we show that Runx1;Runx3 double knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes like Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independent of CBF, suggesting non-transcriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes development of leukemias and other cancers.
Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia predisposition due to transcriptional and DNA repair defects.
Specimen part
View SamplesThis is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state. Overall design: Examination of the Transcriptomic profiles of cells undergoing reprogramming.
RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming.
No sample metadata fields
View SamplesCD133 (Prominin1) is pentaspan transmembrane glycoprotein expressed in several stem cell populations and cancers. Reactivity with an antibody (AC133) to a glycoslyated form of CD133 has been widely used for the enrichment of cells with tumor initiating activity in xenograph transplantation assays. We have found by fluorescence-activated cell sorting that increased AC133 reactivity in human embryonic stem cells, colon cancer and melanoma cells is correlated with increased DNA content and reciprocally, that the least reactive cells are in the G1/G0 portion of the cell cycle. Continued cultivation of cells sorted on the basis of high and low AC133 reactivity results in a normalization of the cell reactivity profiles indicating that cells with low AC133 reactivity can generate highly reactive cells as they resume proliferation. The association of AC133 with actively cycling cells may contribute to the basis for enrichment for tumor initiating activity.
Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines.
No sample metadata fields
View SamplesGene expression profiling of the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminence, and cerebral cortex (CTX) at various embryonic stages (E12.5, E14 and E16).
Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision.
Sex, Specimen part
View SamplesMouse erythroid progenitors (EP) in comparison to granulocyte/monocyte - macrophage progenitors (GMP) from 10 - 16 week old C57/Bl6 - S129Ola (mixed genetic background) purified by flow cytometry
Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E).
No sample metadata fields
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